Exenatide Increases IL-1RA Concentration and Induces Nrf-2-Keap-1 Regulated Anti-oxidant Enzymes: Relevance to ? Cell Function.
Purpose: We have previously demonstrated anti-inflammatory and antioxidant effects of exenatide. We have now hypothesized that exenatide also increases the plasma concentration of IL-1RA, an endogenous anti-inflammatory protein and modulates the Nrf-2-Keap-1-ARE system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress.
Methods: Twenty four obese type 2 diabetic patients on combined oral and insulin therapy were randomized to receive either exenatide 10μg or placebo b.i.d for 12 weeks.
Results: Exenatide induced an increase in IL-1RA concentration by 61% (from 318±53 to 456±88pg/ml, p<0.05). Exenatide treatment also suppressed Keap-1 protein (p<0.05) and increased mRNA expression of NQO-1, GSTP1, HO-1 and p21 and increased NQO-1 protein (p<0.05) in MNC.
Conclusions: Since IL-1RA protects, maintains and stimulates β cell function in the human and Nrf-2-Keap-1-ARE protects the β cell in animals with experimental diabetes, these actions of exenatide may contribute to a potential protective effect on β cell in diabetes.