A novel function of insulin in rat dermis

Area of Science:

• Dermatology
• Endocrinology
• Inflammation Research

Background:

• Inflammation involves edema and pro-inflammatory cytokines, often exacerbated by factors like lipopolysaccharide (LPS).
• Cytokines can lower interstitial fluid pressure (Pif), contributing to edema.
• Insulin's role in inflammation is not fully understood, though it influences cell adhesion via phosphatidylinositol 3-kinase (PI3K).

Purpose of the Study:

• To investigate the novel anti-inflammatory effects of insulin in rat dermis.
• To examine insulin's impact on interstitial fluid pressure (Pif), albumin leakage, and cytokine production during inflammation.
• To explore the role of PI3K in mediating insulin's effects on Pif.

Main Methods:

• Induction of inflammation using lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) in Wistar rats.
• Local and systemic administration of insulin and a glucose-insulin-potassium (GIK) regimen.
• Measurement of Pif, capillary albumin leakage, and pro-inflammatory cytokine levels in skin and serum.
• Inhibition of PI3K with wortmannin to assess its role in insulin's Pif effects.

Main Results:

• Local insulin injection increased Pif in inflamed rat paws, counteracting the pressure drop induced by LPS, TNF-alpha, or IL-1beta.
• The effect of insulin on Pif was significantly reduced by co-administration of a PI3K inhibitor (wortmannin).
• A GIK regimen attenuated edema formation and reduced pro-inflammatory cytokines in serum and skin following LPS or TNF-alpha/IL-1beta challenge.

Conclusions:

• Insulin exhibits a novel anti-inflammatory role in the dermal interstitium during LPS and TNF-alpha/IL-1beta-induced inflammation.
• Insulin may attenuate the decrease in Pif, potentially through PI3K-dependent mechanisms.
• Insulin demonstrates anti-inflammatory properties by inhibiting pro-inflammatory cytokine production.