A novel function of insulin in rat dermis.
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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) 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-alpha or IL-1beta 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-1beta 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-alpha/IL-1beta 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-alpha/IL-1beta. Insulin can attenuate a lowering of Pif possibly via PI3K, and it has an anti-inflammatory effect by inhibiting production of pro-inflammatory cytokines.
Nedrebø
Torbjørn
T
Division for Physiology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. torbjorn.nedrebo@fys.uib.no
Karlsen
Tine V
TV
Salvesen
Gerd S
GS
Reed
Rolf K
RK
D000818:Animals; D020405:Dermis / Q000187:drug effects* / Q000502:physiology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology; D005260:Female; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D008070:Lipopolysaccharides