Exendin-4 in the treatment of Type-2 diabetes and NAFLD
Exendin-4 (Exenatide), a 39-amino acid peptide originally isolated from the oral secretions of the lizard Heloderma suspectum, is an agonist of the glucagon-like-peptide-1 (GLP-1) receptor. Exendin-4 shares a 53% sequence homology with GLP-1. It induces insulin release of insulin after food intake, suppresses the release of glucagon, and slows down gastric emptying, thereby decreasing the rate at which food-derived glucose appears in the bloodstream.
Exendin-4 has a longer half-life than GLP-1 in the plasma, thus making it a more potent insulinotropic agent, and a better candidate for the treatment of type-2 diabetes mellitus. Because Exendin-4 also reduces the liver fat content, it may be beneficial in treating nonalcoholic fatty liver disease (NAFLD), a hepatic disease associated with insulin resistance.
Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism. In the human fetal pancreas, the proliferation and differentiation of endocrine precursor cells into insulin-producing ß-cells can be positively regulated by Exendin-4. Moreover, the peptide accelerates the functional maturation of fetal ß-cells as indicated by the stimulated insulin secretion in response to glucose.
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