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Exenatide Increases IL-1RA Concentration and Induces Nrf-2-Keap-1 Regulated Anti-oxidant Enzymes: Relevance to ? Cell Function.

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Published:15th Jan 2018
Author: Dandona P, Ghanim H, Abuaysheh S, Green K, Dhindsa S, Makdissi A et al.
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Ref.:J Clin Endocrinol Metab. 2018.
DOI:10.1210/jc.2017-02343

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.

 

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