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Integrin alphavbeta3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2008 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 295, no 2, H555-60 p.Article in journal (Refereed) Published
Abstract [en]

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 alpha(v)beta(3). 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 beta(3)-deficient (beta(3)(-/-)) 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 alpha(v)beta(3)-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 alpha(v)beta(3).

Place, publisher, year, edition, pages
2008. Vol. 295, no 2, H555-60 p.
Keyword [en]
glucose-insulin-potassium treatment, tissue fluid balance, inflammation
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-99784DOI: 10.1152/ajpheart.00161.2008ISI: 000258254200014PubMedID: 18552165OAI: oai:DiVA.org:uu-99784DiVA: diva2:208738
Available from: 2009-03-19 Created: 2009-03-19 Last updated: 2011-06-28Bibliographically approved

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Rubin, Kristofer
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Department of Medical Biochemistry and Microbiology
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