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A novel function of insulin in rat dermis

Blackwell Science Inc
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  • Research Papers


In this study we present a novel function of insulin in rat dermis. We investigated local effects of insulin on interstitial fluid pressure (Pif), and capillary albumin leakage and pro-inflammatory cytokine production in skin and serum after intravenous lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) challenge treated with a glucose–insulin–potassium regimen (GIK). The main objective for this study was to investigate anti-inflammatory effects of insulin. Work by others shows that insulin stimulates cell adhesion, and that this effect is dependent upon phosphatidylinositol 3-kinase (PI3K) activity. Cytokines like platelet-derived growth factor BB (PDGF-BB) attenuate lowering of Pif, possibly via PI3K. LPS and pro-inflammatory cytokines contribute to oedema development during acute inflammation by lowering the Pif. Intravenous injection of LPS, TNF-α or IL-1β to Wistar Møller rats caused a lowering of Pif, but after local injection of insulin in the paw, Pif increased back to control values. IL-1β caused a lowering in control from −0.5 ± 0.2 mmHg to −3.0 ± 0.2 mmHg after 20 min (mean ± s.e.m.) (P < 0.05). Within 50 min after insulin injection the pressure was increased to −0.6 ± 0.2 mmHg (P > 0.05 compared with control). Insulin was given together with a PI3K inhibitor (wortmannin) locally in the skin, almost abolishing the effect of insulin on Pif. A GIK regimen was given as a continuous intravenous infusion, significantly attenuating the oedema formation after LPS or TNF-α/IL-1β challenge. The same GIK regimen caused a significant reduction in pro-inflammatory cytokines in serum and in interstitial fluid in skin of endotoxaemic rats. These experiments show a possible role for insulin in the interstitium during inflammation induced by LPS and TNF-α/IL-1β. Insulin can attenuate a lowering of Pif possibly via PI3K, and it has an anti-inflammatory effect by inhibiting production of pro-inflammatory cytokines.

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