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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H555    most recent 00161.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Svendsen, O. S. Articles by Reed, R. K. Search for Related Content PubMed PubMed Citation Articles by Svendsen, O. S. Articles by Reed, R. K.

Integrin _vβ₃ acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction

¹Department of Biomedicine, University of Bergen, Bergen, Norway; ²Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; and ³Department of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway

Submitted 15 February 2008 ; accepted in final form 2 June 2008

The administration of insulin is recommended to patients with severe sepsis and hyperglycemia. Previously, we demonstrated that insulin may have direct anti-inflammatory properties and counteracted fluid losses from the circulation by normalizing the interstitial fluid pressure (P_IF). P_IF is one of the Starling forces determining fluid flux over the capillary wall, and a lowered P_IF is one of the driving forces in early edema formation in inflammatory reactions. Here we demonstrate that insulin restores a lipopolysaccharide (LPS)-lowered P_IF via a mechanism involving integrin _vβ₃. In C57 black mice (n = 6), LPS lowered P_IF from –0.2 ± 0.2 to –1.6 ± 0.3 (P < 0.05) and after insulin averaged –0.8 ± 0.2 mmHg (P = 0.098 compared with after LPS). Corresponding values in wild-type BALB/c mice (n = 5) were –0.8 ± 0.1, –2.1 ± 0.3 (P < 0.05), and –0.8 ± 0.3 mmHg (P < 0.05 compared with LPS) after insulin administration. In BALB/c integrin β₃-deficient (β₃^–/–) mice (n = 6), LPS lowered P_IF from –0.1 ± 0.2 to –1.5 ± 0.3 mmHg (P < 0.05). Insulin did not, however, restore P_IF in these mice (averaged –1.7 ± 0.3 mmHg after insulin administration). Cell-mediated collagen gel contraction can serve as an in vitro model for in vivo measurements of P_IF. Insulin induced _vβ₃-integrin-dependent collagen gel contraction mediated by C2C12 cells. Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of P_IF by a mechanism involving the integrin _vβ₃.

glucose-insulin-potassium treatment; tissue fluid balance; inflammation