| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Internal Medicine and 2 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
Insulin increases glucose uptake through the
translocation of GLUT-4 via a pathway mediated by phosphatidylinositol
3-kinase (PI3K). In contrast, myocardial glucose uptake during
ischemia and hypoxia is stimulated by the translocation of
GLUT-4 to the surface of cardiac myocytes through a PI3K-independent
pathway that has not been characterized. AMP-activated protein kinase (AMPK) activity is also increased by myocardial ischemia, and we examined whether AMPK stimulates glucose uptake and GLUT-4 translocation. In isolated rat ventricular papillary muscles, 5-aminoimidazole-4-carboxyamide-1-
-D-ribofuranoside
(AICAR), an activator of AMPK, as well as cyanide-induced chemical
hypoxia and insulin, increased
2-[3H]deoxyglucose
uptake two- to threefold. Wortmannin, a PI3K inhibitor, did not affect
either the AICAR- or the cyanide-stimulated increase in deoxyglucose
uptake but eliminated the insulin-stimulated increase in deoxyglucose
uptake. Immunofluorescence studies demonstrated translocation of GLUT-4
to the myocyte sarcolemma in response to stimulation with AICAR,
cyanide, or insulin. Preincubation of papillary muscles with the kinase
inhibitor iodotubercidin or adenine
9--D-arabinofuranoside (araA), a precursor of araATP (a
competitive inhibitor of AMPK), decreased AICAR- and cyanide-stimulated glucose uptake but did not affect basal or insulin-stimulated glucose
uptake. In vivo infusion of AICAR caused myocardial AMPK activation and
GLUT-4 translocation in the rat. We conclude that AMPK activation
increases cardiac muscle glucose uptake through translocation of GLUT-4
via a pathway that is independent of PI3K. These findings suggest that
AMPK activation may be important in ischemia-induced
translocation of GLUT-4 in the heart.
GLUT-4; ischemia; adenosine
5'-monophosphate-activated protein kinase; 5-aminoimidazole-4-carboxyamide-1--D-ribofuranoside
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
BOTH INSULIN STIMULATION and ischemia have been shown to cause the translocation of GLUT-4 to the sarcolemma of heart muscle, where it is biologically active (29, 31, 41). Previous studies in heart and skeletal muscle have demonstrated that insulin-mediated translocation of GLUT-4 requires phosphatidylinositol 3-kinase (PI3K) activation and is inhibited by the PI3K inhibitor wortmannin (4, 8, 33). In contrast, ischemia causes translocation of GLUT-4 in the heart through a pathway that is independent of PI3K activation (8). In addition, both hypoxia and contraction also cause GLUT-4 translocation in skeletal muscle through a PI3K-independent pathway (22, 23, 33, 40), suggesting that a common pathway based on metabolic stress is shared between ischemia- and contraction-stimulated translocation of GLUT-4. However, the mechanisms responsible for the translocation of GLUT-4 to the cell surface in response to ischemia-contraction remain to be elucidated.
One potential regulator of the translocation of GLUT-4 in response to
ischemia-contraction is AMP-activated protein kinase (AMPK).
AMPK activity increases in the setting of increased intracellular AMP
and decreased creatine phosphate and is thought to act as a metabolic
stress protein (12, 13, 26). Previous studies have suggested the
possibility that AMPK may play a role in the PI3K-independent signaling
pathway for GLUT-4 translocation in the ischemic heart or contracting
muscle. First, both myocardial ischemia (19, 20) and skeletal
muscle contraction (17, 34, 38) have been shown to cause the activation
of AMPK. Second, studies have shown that activation of AMPK with the
nucleoside 5-aminoimidazole-4-carboxyamide-1--D-ribofuranoside
(AICAR) increases glucose uptake in skeletal muscle, which is not
inhibited by wortmannin (1, 14, 24).
Although AMPK activation leads to increased myocardial fatty acid utilization in the heart (20), the role of AMPK activation in regulating myocardial glucose uptake is not known. In addition, the effects of AMPK activation on GLUT-4 translocation have not been assessed in either heart or skeletal muscle. The present studies were therefore performed to determine whether activation of myocardial AMPK by AICAR causes the translocation of heart GLUT-4 to the sarcolemma, resulting in increased myocardial glucose uptake in vitro. Further studies examined whether inhibition of AMPK affects the activation of myocardial glucose utilization by AICAR or chemical hypoxia. Finally, we also investigated whether AICAR infusion increases AMPK activity and stimulates GLUT-4 translocation in the intact heart in vivo.
| |
EXPERIMENTAL PROCEDURES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
Rat ventricular papillary muscle incubations. The effects of various stimulators and inhibitors of myocardial glucose uptake and phosphorylation were studied in quiescent papillary muscles. Hearts were isolated from fasted (5 h) male Sprague-Dawley rats (300-350 g) and immediately placed in ice-cold Dulbecco's PBS. After the atria were removed, the left ventricle was cut open, and the anterior and posterior papillary muscles (~3-6 mg) were dissected free. The isolated papillary muscles were initially incubated for 30 min at 37°C in PBS containing 1 mM CaCl2, 1 mM MgCl2, 5 mM glucose, and 1% BSA with or without wortmannin (0.5 µM). Incubations were then continued either with no other additions or with insulin (10 mU/ml), potassium cyanide (15 mM), or AICAR (1 mM) for 90 min. 2-[1-3H]deoxyglucose (1 µCi/ml) was present for the final 60 min to estimate rates of glucose uptake and phosphorylation. [U-14C]mannitol (0.1 µCi/ml) was also added to incubations to correct the heart muscle 2-deoxyglucose content for 2-deoxyglucose present in the extracellular fluid space.
After the incubations, papillary muscles were washed three times with ice-cold saline, blotted dry, and weighed. Muscles were then solubilized at 60°C with Soluene-350 (Packard Instrument, Meriden, CT) and subjected to liquid scintillation counting. In experiments determining the effects of AICAR stimulation on myocardial glycogen content, tissue glycogen content was measured in freeze-clamped papillary muscles as previously described (28).
To further elucidate the mechanism of AICAR-stimulated glucose uptake,
inhibitors of different pathways were added to papillary muscles before
incubation with AICAR. The potential roles of protein kinase C (PKC)
activation or adenosine-receptor stimulation in mediating AICAR
stimulation of glucose uptake were studied in papillary muscles
incubated with 0.5 µM calphostin C (a PKC inhibitor) or 10 µM
8-(sulfophenyl)-theophylline (an adenosine-receptor blocker). The
effect of inhibiting AMPK on AICAR- and potassium cyanide-stimulated 2-deoxyglucose uptake was determined by preincubating papillary muscles
for 60 min with the protein kinase inhibitor iodotubercidin (50 µM,
kindly provided by Dr. Gary Lopaschuk, University of Alberta) or with
adenine 9--D-arabinofuranoside (araA, 500 µM), a
precursor of araATP (a competitive inhibitor of AMPK; see Ref. 16).
Muscles were then incubated with media alone or with the addition of
potassium cyanide, AICAR, or insulin, and glucose uptake was estimated
as described above.
Immunofluorescence studies. To determine the subcellular localization of GLUT-4, immunofluorescence studies were performed on papillary muscles incubated as described above and then fixed in 0.5% paraformaldehyde at 4°C. Tissue sections were processed and incubated with rabbit anti-GLUT-4 primary antibody and rhodamine-labeled goat anti-rabbit IgG secondary antibody (Boehringer-Mannheim Biochemicals, Indianapolis, IN) as described previously (41). The slides were then examined using a Zeiss LSM410 confocal microscope. Contrast and brightness settings were chosen so that all pixels were within the linear range. All images are the product of eightfold line averaging.
In vivo AICAR infusion. To confirm the
effect of AICAR on AMPK activity and GLUT-4 translocation in vivo,
awake, unrestrained chronically catheterized rats (18) received
intravenous infusions of either saline or AICAR (40 mg/kg bolus over 2 min followed by a constant infusion of 7.5 mg · kg
1 · min1
for 80 min). The plasma AICAR concentration was determined
spectrophotometrically (9). Glucose was infused intravenously at a
variable rate to maintain the arterial plasma glucose concentration at
euglycemic levels during AICAR infusion because AICAR infusion can
cause hypoglycemia (36).
After the infusion, hearts were removed, and the ventricular muscle was either used for the isolation of intracellular and sarcolemmal membranes for GLUT-4 immunoblot analysis or used to determine AMPK activity. Sarcolemmal and intracellular membrane fractions were isolated by differential and density gradient centrifugation (29, 41). The membrane fractions were then subjected to SDS-PAGE and transferred to polyvinylidene difluoride membranes for immunoblot analysis. Immunoblots were quantified using 125I-labeled protein A (29, 41). To determine AMPK activity, 200 mg of heart tissue were homogenized, and 8 µg of protein from the 2.5-6% polyethylene glycol-precipitated fraction of the homogenate were used in the enzyme assay (20). The AMPK activity was determined by the incorporation of 32P into a synthetic peptide ("SAMS" peptide) as previously described (7).
Statistical analysis. All results are expressed as means ± SE. Differences in rates of glucose uptake were analyzed using ANOVA and the Newman-Keuls test for post hoc comparisons. Differences in the AMPK activity and subcellular distribution of GLUT-4 were assessed by Student's t-test. A value of P < 0.05 was considered statistically significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
Incubation of rat ventricular papillary muscles with AICAR (1 mM)
increased the rate of 2-deoxyglucose uptake twofold
(P < 0.05; Fig.
1). This increase in 2-deoxyglucose uptake
was similar to that seen for papillary muscles incubated with insulin
at a concentration that maximally stimulates glucose uptake. The
addition of cyanide to papillary muscles resulted in a threefold
increase in 2-deoxyglucose uptake compared with control papillary
muscles (P < 0.01). The uptake of
glucose in papillary muscles incubated with cyanide was also somewhat
greater than that for papillary muscles incubated with either insulin
or AICAR (P < 0.05). To demonstrate
that the AMPK-stimulated increase in 2-deoxyglucose uptake is not
mediated by PI3K activation, papillary muscles were incubated with
wortmannin before the addition of AICAR, cyanide, or insulin.
Wortmannin inhibited insulin-mediated myocardial 2-deoxyglucose uptake
but did not attenuate the increase in 2-deoxyglucose uptake mediated by
either AICAR or cyanide.
|
Figure 2 demonstrates the subcellular
distribution of GLUT-4 determined by immunofluorescence confocal
microscopy. Although there is a relatively homogeneous distribution of
GLUT-4 throughout the individual cardiac myocytes in papillary muscles
incubated with glucose alone, the addition of AICAR, cyanide, or
insulin resulted in a greater amount of GLUT-4 localizing to the
sarcolemma of the myocytes. These findings indicate that AICAR causes
translocation of GLUT-4 to the cardiac myocyte cell surface to a
similar degree as known stimulators of translocation (i.e., insulin and
ischemia; see Refs. 29 and 41).
|
Both activation of PKC and adenosine-receptor activation have been suggested to play a role in the translocation of GLUT-4 and increased muscle glucose uptake in response to increased work or ischemia (15). However, incubation of papillary muscles with the PKC inhibitor calphostin C did not affect the increase in 2-deoxyglucose uptake mediated by AICAR (Fig. 1). In addition, blocking the adenosine receptor with 8-(sulfophenyl)-theophylline did not decrease the AICAR-stimulated 2-deoxyglucose uptake in ventricular papillary muscles.
AICAR stimulation results in an increase in skeletal muscle utilization
of both glucose and fatty acids (24). To determine whether AICAR
stimulation of cardiac muscle AMPK would result in an increase in
glucose uptake in the presence of fatty acids, papillary muscles were
incubated as described above with glucose (5 mM) either in the presence
or in the absence of palmitate (0.5 mM) bound to 5% BSA. Under
unstimulated conditions, the rate of glucose uptake was reduced by
~30% by the addition of palmitate (Table
1). AICAR (1 mM) increased glucose uptake
in papillary muscles almost twofold in both the absence and presence of
free fatty acid. In addition, incubation of papillary muscles with AICAR had no significant effect on the tissue content of glycogen (Table 1), which is in keeping with our recent findings of no change in
skeletal muscle glycogen content in rats infused with AICAR in vivo
(1).
|
To determine if inhibition of AMPK decreases glucose uptake under
conditions of chemical hypoxia, AICAR, or insulin stimulation, papillary muscles were preincubated with a precursor of araATP, a
competitive inhibitor of AMPK (16). Preincubation of papillary muscles
with araA (500 µM) had no effect on glucose uptake under control
conditions (Fig. 3). Similarly, araA had no
effect on insulin-stimulated glucose uptake. However, preincubation
with araA significantly decreased the uptake of glucose in papillary muscles subjected to cyanide-induced chemical hypoxia and tended to
decrease AICAR-stimulated glucose uptake. Furthermore, preincubation of
papillary muscles with varying concentrations of araA resulted in a
significant dose-dependent decrease in AICAR-stimulated glucose uptake
(Fig. 3).
|
Previous studies have also demonstrated that iodotubercidin can inhibit
AMPK activation (16). To determine if iodotubercidin can inhibit
AMPK-mediated increases in glucose uptake, papillary muscles were
preincubated with iodotubercidin before stimulation with AICAR,
cyanide, or insulin. Iodotubercidin (50 µM) decreased cyanide- and
AICAR-stimulated glucose uptake to basal levels. In contrast,
iodotubercidin had no effect on either basal glucose utilization or
insulin-stimulated utilization (Fig. 4).
Therefore, two different inhibitors of AMPK, araA and iodotubercidin,
can inhibit both AICAR- and cyanide-stimulated glucose uptake.
|
AICAR was infused in vivo in awake, unrestrained rats to confirm that
AICAR activates AMPK and translocates GLUT-4 in the intact heart. The
intravenous infusion of AICAR in vivo resulted in an arterial plasma
AICAR concentration (0.89 ± 0.07 mM) that was similar to that used
for the in vitro incubations (1 mM). The mean arterial blood pressure
(115 ± 3 vs. 111 ± 17 mmHg) and heart rate (409 ± 13 vs.
431 ± 19 min1) were
similar for rats infused with AICAR and rats infused with saline. AICAR
stimulated whole body glucose uptake, and a steady-state glucose
infusion rate of 134 ± 11 µmol · kg1 · min1
was required to maintain euglycemia. The myocardial AMPK activity in
AICAR-infused rats was approximately threefold higher than that for
saline-infused animals (Fig. 5;
P < 0.0005). In addition, AICAR
infusion caused an increase in the sarcolemmal content of GLUT-4 with a
concomitant decrease in the intracellular content of GLUT-4 as
determined by membrane fractionation, resulting in a 57% increase in
the sarcolemmal-to-intracellular content ratio for GLUT-4 (Fig.
6; P < 0.05).
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
The present study demonstrates that AICAR, a specific activator of AMPK (6), causes translocation of GLUT-4 to the surface of cardiac myocytes and increases heart muscle glucose uptake. In addition, like hypoxia-ischemia, AICAR causes GLUT-4 translocation through a pathway that does not require activation of PI3K. In addition, both AICAR- and hypoxia-mediated glucose uptake, but not insulin-stimulated glucose uptake, were inhibited by the addition of either araA or iodotubercidin, inhibitors of AMPK. Given the fact that both AICAR and ischemia cause activation of AMPK (6, 19, 20) and translocation of GLUT-4 (31, 41), these results support a role for AMPK activation in the PI3K-independent translocation of GLUT-4 in response to metabolic stressors.
AICAR is taken up by cells, phosphorylated, and accumulates as 5-aminoimidazole-4-carboxyamide-ribonucleoside monophosphate, mimicking the ability of AMP to activate AMPK (6). Infusion of AICAR in vivo has previously been shown to cause hypoglycemia in mice (36). It was hypothesized that the hypoglycemia was caused by inhibition of gluconeogenesis, a known effect of AMPK activation (37). Subsequent studies in perfused rat hindlimbs demonstrated that AICAR increases skeletal muscle glucose uptake in the presence of maximally stimulating doses of insulin (24), suggesting that the hypoglycemic effect of AICAR is also due to increased cellular glucose uptake. In addition, recent studies have also demonstrated that AICAR-mediated activation of AMPK stimulates skeletal muscle glucose uptake (1, 14). However, these previous studies did not investigate whether AICAR increased muscle glucose uptake by stimulating the translocation of GLUT-4. Thus the present study is not only the first to demonstrate that AICAR increases glucose uptake in the heart but also the first to demonstrate that AICAR causes translocation of GLUT-4 to the cell surface in muscle tissue.
AMP activates AMPK through both covalent and noncovalent mechanisms (13). Increased AMP concentrations cause AMPK kinase to phosphorylate AMPK, thereby increasing its activity. In addition, an increased AMP concentration allosterically activates the enzyme. Myocardial ischemia (27) and skeletal muscle contraction (17) increase the intracellular content of AMP with a concomitant stimulation of AMPK activity (17, 19). AMPK kinase activity is presumably increased by ischemia or muscle contraction, although it has not been studied.
Given the responsiveness of AMPK to the energy charge of the cell, the enzyme has been described as a "fuel gauge" for controlling the supply of energy providing substrates to the cell (12). In keeping with this role, AMPK activation results in a cellular shift favoring catabolic metabolic pathways over anabolic pathways. Specifically, AMPK causes phosphorylation and inactivation of acetyl-CoA carboxylase (3, 39), with a resulting decrease in malonyl-CoA and a shift from lipogenesis (30) to fatty acid oxidation (19, 20). Previous studies suggested that AICAR also stimulates glycogen mobilization and phosphorylase activity in skeletal muscle but did not measure glycogen content directly (42). However, in the present study, the glycogen content of papillary muscles was not affected by AICAR. Similarly, we have recently demonstrated that AICAR infusion does not affect the glycogen content of skeletal muscle (1). Our findings suggest that either phosphorylase is not affected in cardiac muscle or more complex interactions between glucose uptake and increased glycogen breakdown occur with AMPK activation. On the basis of our results, AMPK activation would appear to primarily increase glucose transport rather than affect glycogen mobilization.
The current study, as well as studies in skeletal muscle (1, 14), demonstrates that AICAR stimulation of glucose uptake is not attenuated by PI3K inhibition. Our findings also confirm previous studies that demonstrate that insulin-mediated glucose uptake is inhibited by the PI3K inhibitor wortmannin but that hypoxia-stimulated glucose uptake does not decrease with PI3K inhibition (8, 33). Although PI3K activation is not required for ischemia-contraction-stimulated or AICAR-stimulated glucose uptake, it remains unclear whether insulin stimulation and ischemia-contraction stimulation share a common distal pathway that is responsible for GLUT-4 translocation. Recent studies have shown that the protein kinase Akt is activated by insulin stimulation via PI3K but is not affected by skeletal muscle contraction (2), suggesting that, if there is a common pathway, it is further downstream than Akt. Insulin and ischemia-contraction may also cause the translocation of separate pools of intracellular GLUT-4-containing vesicles to the cell surface (5) or may trigger translocation of a common intracellular GLUT-4 pool through distinct distal pathways.
Several other PI3K-independent pathways have been proposed to be responsible for ischemia-contraction-stimulated GLUT-4 translocation, including PKC activation, Jun NH2-terminal kinase activation, p38 kinase activation, nitric oxide release, and adenosine-receptor stimulation (for review, see Ref. 15). Stimulation of cells with phorbol esters causes translocation of GLUT-4, which can be blocked by PKC inhibition (11, 25). However, the present studies suggest that PKC activation does not play a role as a downstream mediator of AMPK-mediated GLUT-4 translocation, which is in keeping with previous studies demonstrating that phorbol esters stimulate GLUT-4 translocation by a pathway that is distinct from hypoxia (11). In addition, AICAR can increase adenosine content (10), which has been shown in some studies to increase glucose uptake during insulin stimulation (21, 35), raising the possibility that adenosine-receptor stimulation was responsible for increased glucose uptake. However, adenosine-receptor blockade with 8-(sulfophenyl)-theophylline did not affect AICAR-mediated increases in glucose uptake in the present study.
Our experiments demonstrated inhibition of AICAR- and cyanide-stimulated glucose uptake with the serine/threonine protein kinase inhibitor iodotubercidin as well as a precursor of araATP, a competitive, but nonspecific, inhibitor of AMPK. In contrast, neither inhibitor affected insulin-stimulated glucose uptake. These findings provide further support for the role of AMPK activation in both AICAR- and cyanide-stimulated glucose uptake. Our results are also in keeping with preliminary studies demonstrating that iodotubercidin decreases postischemic myocardial AMPK activation (32). We cannot exclude the possibility that mechanisms other than AMPK activation may contribute to the cyanide-stimulated translocation of GLUT-4 and increase in glucose uptake in the present study. However, our experiments excluded the possible influences of adenosine receptor stimulation and PKC or PI3K activation. Further evaluation of the role of AMPK in ischemia-contraction-mediated translocation of GLUT-4 will require the development of inhibitors/activators of AMPK with greater specificity or the use of systems in which AMPK is overexpressed or deleted.
Chemical hypoxia appeared to stimulate glucose uptake and phosphorylation to a somewhat greater extent than AICAR (~17% when all of the experiments were combined). Because of the size of isolated papillary muscle, we were unable to determine if AMPK was activated to a greater extent with cyanide than with AICAR. However, AICAR is known to stimulate liver AMPK in vitro (6), and our studies demonstrate that AICAR infusion in vivo activates myocardial AMPK in whole heart. It is possible that other pathways are also activated in cyanide-stimulated heart muscle. Furthermore, although AICAR activation of AMPK stimulates the translocation of GLUT-4, it would not necessarily increase the metabolic demand for glucose, which would conceivably affect the transport and phosphorylation of glucose. This is in contrast to physiological (e.g., exercise) and pathophysiological (e.g., ischemia) states where muscle AMPK activation occurs in response to increased energy needs.
In summary, the present studies support the novel hypothesis that metabolic stressors, such as ischemia, cause the translocation of myocardial GLUT-4 through a pathway that includes AMPK. This pathway is distinct from the insulin-stimulated pathway that requires PI3K activation. The subsequent steps responsible for GLUT-4 translocation in response to changes in the energy charge of the cell require definition.
| |
ACKNOWLEDGEMENTS |
|---|
We acknowledge the helpful advice of Dr. Michael Caplan.
| |
FOOTNOTES |
|---|
This work was funded, in part, by a grant-in-aid from the American Heart Association and National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK-40936. R. R. Russell III was the recipient of an individual National Research Service Award Postdoctoral Fellowship from the National Heart, Lung, and Blood Institute (HL-09447).
Portions of this study were presented in abstract form at the 58th Annual Scientific Sessions of the American Diabetes Association, June 13-16, 1998, Chicago, IL.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: L. H. Young, Division of Cardiology, Yale Univ. School of Medicine, 333 Cedar St., 3 FMP, New Haven, CT 06520 (E-mail: lawrence.young{at}yale.edu).
Received 31 December 1998; accepted in final form 13 April 1999.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Bergeron, R.,
R. R. Russell,
L. H. Young,
J.-M. Ren,
M. Marcucci,
A. Lee,
and
G. I. Shulman.
Effect of AMPK activation on muscle glucose metabolism in conscious rats.
Am. J. Physiol.
276 (Endocrinol. Metab. 39):
E938-E944,
1999
2.
Brozinick, J. T., Jr.,
and
M. J. Birnbaum.
Insulin, but not contraction, activates Akt/PKB in isolated rat skeletal muscle.
J. Biol. Chem.
273:
14679-14682,
1998
3.
Carling, D.,
P. R. Clarke,
V. A. Zammit,
and
D. G. Hardie.
Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities.
Eur. J. Biochem.
186:
129-136,
1989[Medline].
4.
Clarke, J. F.,
P. W. Young,
K. Yonewzawa,
M. Kasuga,
and
G. D. Holman.
Inhibition of the translocation of GLUT1 and GLUT4 in 3T3-L1 cells by the phosphatidylinositol 3-kinase inhibitor, wortmannin.
Biochem. J.
300:
631-635,
1994.
5.
Coderre, L.,
K. V. Kandror,
G. Vallega,
and
P. F. Pilch.
Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.
J. Biol. Chem.
270:
27584-27588,
1995
6.
Corton, J. M.,
J. G. Gillespie,
S. A. Hawley,
and
D. G. Hardie.
5-Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?
Eur. J. Biochem.
229:
558-565,
1995[Medline].
7.
Davies, S. P.,
D. Carling,
and
D. G. Hardie.
Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay.
Eur. J. Biochem.
186:
123-128,
1989[Medline].
8.
Egert, S.,
N. Nguyen,
F. C. Brosius III,
and
M. Schwaiger.
Effects of wortmannin on insulin- and ischemia-induced stimulation of GLUT4 translocation and FDG uptake in perfused rat hearts.
Cardiovasc. Res.
35:
283-293,
1997
9.
Fujitaki, J. M.,
T. M. Sandoval,
L. A. Lembach,
and
R. Dixon.
Spectrophotometric determination of acadesine (AICA-riboside) in plasma using a diazotization coupling technique with N-(1-napthyl)ethylenediamine.
J. Biochem. Biophys. Methods
29:
143-148,
1994[Medline].
10.
Gruber, H. E.,
M. E. Hoffer,
D. R. McAllister,
P. K. Laikind,
T. A. Lane,
G. W. Schmidt-Schoenbein,
and
R. L. Engler.
Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects of flow, granulocytes, and injury.
Circulation
80:
1400-1411,
1989
11.
Hansen, P. A.,
J. A. Corbett,
and
J. O. Holloszy.
Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathway.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E28-E36,
1997
12.
Hardie, D. G.,
and
D. Carling.
The AMP-activated protein kinase: fuel gauge of the mammalian cell?
Eur. J. Biochem.
246:
259-273,
1997[Medline].
13.
Hardie, D. G.,
D. Carling,
and
N. Halford.
Roles of the Snf1/Rkin1/AMP-activated protein kinase family in the response to environmental and nutritional stress.
Semin. Cell Biol.
5:
409-416,
1994[Medline].
14.
Hayashi, T.,
M. F. Hirshman,
E. J. Kurth,
W. W. Winder,
and
L. J. Goodyear.
Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport.
Diabetes
47:
1369-1373,
1998[Abstract].
15.
Hayashi, T.,
J. F. P. Wojtaszewski,
and
L. J. Goodyear.
Exercise regulation of glucose transport in skeletal muscle.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E1039-E1051,
1997.
16.
Henin, N.,
M. F. Vincent,
and
G. Van den Berghe.
Stimulation of rat liver AMP-activated protein kinase by AMP analogues.
Biochim. Biophys. Acta
1290:
197-203,
1996[Medline].
17.
Hutber, C. A.,
D. G. Hardie,
and
W. W. Winder.
Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E262-E266,
1997
18.
Jacob, R.,
X. Hu,
D. Niederstock,
S. Hasan,
P. H. McNulty,
R. S. Sherwin,
and
L. H. Young.
IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids.
Am. J. Physiol.
270 (Endocrinol. Metab. 33):
E60-E66,
1996
19.
Kudo, N.,
A. J. Barr,
R. L. Barr,
S. Desai,
and
G. D. Lopaschuk.
High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5'-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase.
J. Biol. Chem.
270:
17513-17520,
1995
20.
Kudo, N.,
J. G. Gillespie,
L. Kung,
L. A. Witters,
R. Schulz,
A. S. Clanachan,
and
G. D. Lopaschuk.
Characterization of 5'AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemia.
Biochim. Biophys. Acta
1301:
67-75,
1996[Medline].
21.
Law, W. R.,
and
R. M. Raymond.
Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo.
Am. J. Physiol.
254 (Heart Circ. Physiol. 23):
H970-H975,
1988
22.
Lee, A. D.,
P. A. Hansen,
and
J. O. Holloszy.
Wortmannin inhibits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.
FEBS Lett.
361:
51-54,
1995[Medline].
23.
Lund, S.,
G. D. Holman,
O. Schmitz,
and
O. Pedersen.
Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.
Proc. Natl. Acad. Sci. USA
92:
5817-5821,
1995
24.
Merrill, G. F.,
E. J. Kurth,
D. G. Hardie,
and
W. W. Winder.
AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E1107-E1112,
1997.
25.
Nishimura, H.,
and
I. A. Simpson.
Staurosporine inhibits phorbol 12-myristate 13-acetate- and insulin-stimulated translocation of GLUT1 and GLUT4 glucose transporters in rat adipose cells.
Biochem. J.
302:
271-277,
1994.
26.
Ponticos, M.,
Q. L. Lu,
J. E. Morgan,
D. G. Hardie,
T. A. Partridge,
and
D. Carling.
Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle.
EMBO J.
17:
1688-1699,
1998[Medline].
27.
Reibel, D. K.,
and
M. J. Rovetto.
Myocardial ATP synthesis and mechanical function following oxygen deficiency.
Am. J. Physiol.
234 (Heart Circ. Physiol. 3):
H620-H624,
1978
28.
Russell, R. R.,
G. W. Cline,
P. H. Guthrie,
G. W. Goodwin,
G. I. Shulman,
and
H. Taegtmeyer.
Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart: a three tracer study of glycolysis, glycogen metabolism and glucose oxidation.
J. Clin. Invest.
100:
2892-2899,
1997[Medline].
29.
Russell, R. R.,
Y. Renfu,
M. J. Caplan,
X. Hu,
J. Ren,
G. I. Shulman,
A. J. Sinusas,
and
L. H. Young.
Additive effects of hyperinsulinemia and ischemia on myocardial GLUT1 and GLUT4 translocation in vivo.
Circulation
98:
2180-2186,
1998
30.
Sullivan, J. E.,
K. J. Brocklehurst,
A. E. Marley,
F. Carey,
D. Carling,
and
R. K. Beri.
Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase.
FEBS Lett.
353:
33-36,
1994[Medline].
31.
Sun, D.,
N. Nguyen,
T. R. DeGrado,
M. Schwaiger,
and
F. C. Brosius III.
Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes.
Circulation
89:
793-798,
1994
32.
Taniguchi, M.,
J. Y. Altarejos,
A. S. Clanachan,
and
G. D. Lopaschuk.
Inhibition of 5'AMP-activated protein kinase inhibits fatty acid oxidation and improves functional recovery of ischemic hearts (Abstract).
Circulation
98, Suppl. I:
I759,
1998.
33.
Tsakiridis, T.,
M. Vranic,
and
A. Klip.
Phosphatidylinositol 3-kinase and the actin network are not required for the stimulation of glucose transport caused by mitochondrial uncoupling: comparison with insulin action.
Biochem. J.
309:
1-5,
1995.
34.
Vavvas, D.,
A. Apazidis,
A. K. Saha,
J. Gamble,
A. Patel,
B. E. Kemp,
L. A. Witters,
and
N. B. Ruderman.
Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle.
J. Biol. Chem.
272:
13255-13261,
1997
35.
Vergauwen, L.,
P. Hespel,
and
E. A. Richter.
Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.
J. Clin. Invest.
93:
974-981,
1994.
36.
Vincent, M. F.,
M. D. Erion,
H. E. Gruber,
and
G. Van den Berghe.
Hypoglycemic effect of AICAriboside in mice.
Diabetologia
39:
1148-1155,
1996[Medline].
37.
Vincent, M. F.,
P. J. Marangos,
H. E. Gruber,
and
G. Van den Berghe.
Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.
Diabetes
40:
1259-1266,
1991[Abstract].
38.
Winder, W. W.,
and
D. G. Hardie.
Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise.
Am. J. Physiol.
270 (Endocrinol. Metab. 33):
E299-E304,
1996
39.
Winder, W. W.,
H. A. Wilson,
D. G. Hardie,
B. B. Rasmussen,
C. A. Hutber,
G. B. Call,
R. D. Clayton,
L. M. Conley,
S. Yoon,
and
B. Zhou.
Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A.
J. Appl. Physiol.
82:
219-225,
1997
40.
Yeh, J. I.,
E. A. Gulve,
L. Rameh,
and
M. J. Birnbaum.
The effects of wortmannin on rat skeletal muscle: dissociation of signaling pathways for insulin- and contraction-activated hexose transport.
J. Biol. Chem.
270:
2107-2111,
1995
41.
Young, L. H.,
Y. Renfu,
R. Russell,
X. Hu,
M. Caplan,
J. Ren,
G. I. Shulman,
and
A. J. Sinusas.
Low flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
Circulation
95:
415-422,
1997
42.
Young, M. E.,
G. K. Radda,
and
B. Leighton.
Activation of glycogen phosphorylase and glycogenolysis in rat skeletal muscle by AICAR
an activator of AMP-activated protein kinase.
FEBS Lett.
382:
43-47,
1996[Medline].
This article has been cited by other articles:
|
|
 |
|
  A. Lim, S.-H. Park, J.-W. Sohn, J.-H. Jeon, J.-H. Park, D.-K. Song, S.-H. Lee, and W.-K. Ho Glucose Deprivation Regulates KATP Channel Trafficking via AMP-Activated Protein Kinase in Pancreatic {beta}-Cells Diabetes, December 1, 2009; 58(12): 2813 - 2819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Riera, M. N. Galardo, E. H. Pellizzari, S. B. Meroni, and S. B. Cigorraga Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E907 - E914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, J. Li, and J. Ren UCF-101 mitigates streptozotocin-induced cardiomyocyte dysfunction: role of AMPK Am J Physiol Endocrinol Metab, October 1, 2009; 297(4): E965 - E973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hue and H. Taegtmeyer The Randle cycle revisited: a new head for an old hat Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E578 - E591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Saeedi, V. V. Saran, S. S. Y. Wu, E. S. Kume, K. Paulson, A. P. K. Chan, H. L. Parsons, R. B. Wambolt, J. R. B. Dyck, R. W. Brownsey, et al. AMP-activated protein kinase influences metabolic remodeling in H9c2 cells hypertrophied by arginine vasopressin Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1822 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Zwetsloot, L. M. Westerkamp, B. F. Holmes, and T. P. Gavin AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise J. Physiol., December 15, 2008; 586(24): 6021 - 6035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-O. Stenslokken, S. Ellefsen, J. A. W. Stecyk, M. B. Dahl, G. E. Nilsson, and J. Vaage Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius) Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1803 - R1814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Puthanveetil, F. Wang, G. Kewalramani, M. S. Kim, E. Hosseini-Beheshti, N. Ng, W. Lau, T. Pulinilkunnil, M. Allard, A. Abrahani, et al. Cardiac glycogen accumulation after dexamethasone is regulated by AMPK Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1753 - H1762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Saeedi, H. L. Parsons, R. B. Wambolt, K. Paulson, V. Sharma, J. R. B. Dyck, R. W. Brownsey, and M. F. Allard Metabolic actions of metformin in the heart can occur by AMPK-independent mechanisms Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2497 - H2506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Cammisotto, I. Londono, D. Gingras, and M. Bendayan Control of glycogen synthase through ADIPOR1-AMPK pathway in renal distal tubules of normal and diabetic rats Am J Physiol Renal Physiol, April 1, 2008; 294(4): F881 - F889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Omar, H. Fraser, and A. S. Clanachan Ischemia-induced activation of AMPK does not increase glucose uptake in glycogen-replete isolated working rat hearts Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1266 - H1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Folmes, L. A. Witters, M. F. Allard, M. E. Young, and J. R. B. Dyck The AMPK {gamma}1 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3456 - H3464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Kim, S.-N. Jung, K. H. Son, S. R. Kim, T. Y. Ha, M. G. Park, I. G. Jo, J. G. Park, W. Choe, S.-S. Kim, et al. Antidiabetes and Antiobesity Effect of Cryptotanshinone via Activation of AMP-Activated Protein Kinase Mol. Pharmacol., July 1, 2007; 72(1): 62 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, H. He, and J. A. Balschi Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H457 - H466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Iwasaki, M. Nishiyama, T. Taguchi, M. Kambayashi, M. Asai, M. Yoshida, T. Nigawara, and K. Hashimoto Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1899 - E1905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pelletier and L. Coderre Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1325 - E1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jaswal, M. Gandhi, B. A. Finegan, J. R. B. Dyck, and A. S. Clanachan p38 mitogen-activated protein kinase mediates adenosine-induced alterations in myocardial glucose utilization via 5'-AMP-activated protein kinase Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1978 - H1985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. B. Davey, P. B. Garlick, A. Warley, and R. Southworth Immunogold labeling study of the distribution of GLUT-1 and GLUT-4 in cardiac tissue following stimulation by insulin or ischemia Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H2009 - H2019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Allard, H. L. Parsons, R. Saeedi, R. B. Wambolt, and R. Brownsey AMPK and metabolic adaptation by the heart to pressure overload Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H140 - H148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Southworth, K. A. B. Davey, A. Warley, and P. B. Garlick A reevaluation of the roles of hexokinase I and II in the heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H378 - H386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. W. Dolinsky and J. R. B. Dyck Role of AMP-activated protein kinase in healthy and diseased hearts Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2557 - H2569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zarrinpashneh, K. Carjaval, C. Beauloye, A. Ginion, P. Mateo, A.-C. Pouleur, S. Horman, S. Vaulont, J. Hoerter, B. Viollet, et al. Role of the {alpha}2-isoform of AMP-activated protein kinase in the metabolic response of the heart to no-flow ischemia Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2875 - H2883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fujii, N. Jessen, and L. J. Goodyear AMP-activated protein kinase and the regulation of glucose transport Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E867 - E877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jaswal, M. Gandhi, B. A. Finegan, J. R. B. Dyck, and A. S. Clanachan Effects of adenosine on myocardial glucose and palmitate metabolism after transient ischemia: role of 5'-AMP-activated protein kinase Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1883 - H1892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, D. L. Coven, E. J. Miller, X. Hu, M. E. Young, D. Carling, A. J. Sinusas, and L. H. Young Activation of AMPK {alpha}- and {gamma}-isoform complexes in the intact ischemic rat heart Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1927 - H1934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bertrand, A. Ginion, C. Beauloye, A. D. Hebert, B. Guigas, L. Hue, and J.-L. Vanoverschelde AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H239 - H250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. M. Soltys, S. Kovacic, and J. R. B. Dyck Activation of cardiac AMP-activated protein kinase by LKB1 expression or chemical hypoxia is blunted by increased Akt activity Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2472 - H2479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sakamoto, E. Zarrinpashneh, G. R. Budas, A.-C. Pouleur, A. Dutta, A. R. Prescott, J.-L. Vanoverschelde, A. Ashworth, A. Jovanovic, D. R. Alessi, et al. Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPK{alpha}2 but not AMPK{alpha}1 Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E780 - E788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, M. Frederich, H. He, and J. A. Balschi Relationship between 5-aminoimidazole-4-carboxamide-ribotide and AMP-activated protein kinase activity in the perfused mouse heart Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1235 - H1243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Smith, P. B. Patil, and J. S. Fisher AICAR and hyperosmotic stress increase insulin-stimulated glucose transport J Appl Physiol, September 1, 2005; 99(3): 877 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. An, G. Kewalramani, D. Qi, T. Pulinilkunnil, S. Ghosh, A. Abrahani, R. Wambolt, M. Allard, S. M. Innis, and B. Rodrigues {beta}-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1120 - E1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O. Eijnde, W. Derave, J. F. P. Wojtaszewski, E. A. Richter, and P. Hespel AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation J Appl Physiol, April 1, 2005; 98(4): 1228 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, X. Hu, P. Selvakumar, R. R. Russell III, S. W. Cushman, G. D. Holman, and L. H. Young Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E834 - E841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shearer, P. T. Fueger, J. N. Rottman, D. P. Bracy, P. H. Martin, and D. H. Wasserman AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E871 - E877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. G. S. Oliveira, M. Ueno, C. T. de Souza, M. Pereira-da-Silva, A. L. Gasparetti, R. M. N. Bezzera, L. C. Alberici, A. E. Vercesi, M. J. A. Saad, and L. A. Velloso Cold-induced PGC-1{alpha} expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E686 - E695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. McFalls, M. Hou, R. J. Bache, A. Best, D. Marx, J. Sikora, and H. B. Ward Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1328 - H1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shearer, P. T. Fueger, B. Vorndick, D. P. Bracy, J. N. Rottman, J. A. Clanton, and D. H. Wasserman AMP Kinase-Induced Skeletal Muscle Glucose But Not Long-Chain Fatty Acid Uptake Is Dependent on Nitric Oxide Diabetes, June 1, 2004; 53(6): 1429 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Walker, H. B. Jijon, T. Churchill, M. Kulka, and K. L. Madsen Activation of AMP-activated protein kinase reduces cAMP-mediated epithelial chloride secretion Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G850 - G860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Coven, X. Hu, L. Cong, R. Bergeron, G. I. Shulman, D. G. Hardie, and L. H. Young Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E629 - E636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thamotharan, R. A. McKnight, S. Thamotharan, D. J. Kao, and S. U. Devaskar Aberrant insulin-induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E901 - E914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Longnus, R. B. Wambolt, H. L. Parsons, R. W. Brownsey, and M. F. Allard 5-Aminoimidazole-4-carboxamide 1-beta -D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R936 - R944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.J. Zuurbier Postischemic Myocardial Metabolism Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 59 - 65. [PDF]
|
|
|
|
|
|
J. Peart, L. Willems, and J. P. Headrick Receptor and non-receptor-dependent mechanisms of cardioprotection with adenosine Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H519 - H527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stoppani, A. L. Hildebrandt, K. Sakamoto, D. Cameron-Smith, L. J. Goodyear, and P. D. Neufer AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1239 - E1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sakoda, T. Ogihara, M. Anai, M. Fujishiro, H. Ono, Y. Onishi, H. Katagiri, M. Abe, Y. Fukushima, N. Shojima, et al. Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1239 - E1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. McFalls, B. Murad, J.-S. Liow, M. C. Gannon, H. C. Haspel, A. Lange, D. Marx, J. Sikora, and H. B. Ward Glucose uptake and glycogen levels are increased in pig heart after repetitive ischemia Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H205 - H211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Longnus, R. B. Wambolt, R. L. Barr, G. D. Lopaschuk, and M. F. Allard Regulation of myocardial fatty acid oxidation by substrate supply Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1561 - H1567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zheng, P. S. MacLean, S. C. Pohnert, J. B. Knight, A. L. Olson, W. W. Winder, and G. L. Dohm Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase J Appl Physiol, September 1, 2001; 91(3): 1073 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Kaushik, M. E. Young, D. J. Dean, T. G. Kurowski, A. K. Saha, and N. B. Ruderman Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle: effects of AICAR Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E335 - E340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Peltoniemi, H. Yki-Järvinen, V. Oikonen, A. Oksanen, T. O. Takala, T. Rönnemaa, M. Erkinjuntti, M. J. Knuuti, and P. Nuutila Resistance to Exercise-Induced Increase in Glucose Uptake During Hyperinsulinemia in Insulin-Resistant Skeletal Muscle of Patients With Type 1 Diabetes Diabetes, June 1, 2001; 50(6): 1371 - 1377. [Abstract] [Full Text]
|
|
|
|
|
|
N. Musi, N. Fujii, M. F. Hirshman, I. Ekberg, S. Fröberg, O. Ljungqvist, A. Thorell, and L. J. Goodyear AMP-Activated Protein Kinase (AMPK) Is Activated in Muscle of Subjects With Type 2 Diabetes During Exercise Diabetes, May 1, 2001; 50(5): 921 - 927. [Abstract] [Full Text]
|
|
|
|
|
|
N. Musi, T. Hayashi, N. Fujii, M. F. Hirshman, L. A. Witters, and L. J. Goodyear AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle Am J Physiol Endocrinol Metab, May 1, 2001; 280(5): E677 - E684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bergeron, S. F. Previs, G. W. Cline, P. Perret, R. R. Russell III, L. H. Young, and G. I. Shulman Effect of 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats Diabetes, May 1, 2001; 50(5): 1076 - 1082. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Beauloye, L. Bertrand, U. Krause, A.-S. Marsin, T. Dresselaers, F. Vanstapel, J.-L. Vanoverschelde, and L. Hue No-Flow Ischemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH Circ. Res., March 16, 2001; 88(5): 513 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higaki, M. F. Hirshman, N. Fujii, and L. J. Goodyear Nitric Oxide Increases Glucose Uptake Through a Mechanism That Is Distinct From the Insulin and Contraction Pathways in Rat Skeletal Muscle Diabetes, February 1, 2001; 50(2): 241 - 247. [Abstract] [Full Text]
|
|
|
|
|
|
Z.-P. Chen, G. K. McConell, B. J. Michell, R. J. Snow, B. J. Canny, and B. E. Kemp AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1202 - E1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhou, B.-Z. Lin, S. Coughlin, G. Vallega, and P. F. Pilch UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E622 - E629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Ojuka, L. A. Nolte, and J. O. Holloszy Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro J Appl Physiol, March 1, 2000; 88(3): 1072 - 1075. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
P < 0.01 compared with the other groups. No. of experiments is indicated in
parentheses.
