Possible mechanisms and molecular signaling of incretins against the development of type 2 diabetes mellitus

Abstract

Increasing number of cases with diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling the blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gut-derived hormones that trigger the post-meal secretion of insulin, are a well-known family of blood glucose modulators. Currently, incretin medications, including glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are extensively used to treat patients with type 2 diabetes mellitus (T2D). Several experimental and clinical studies illustrate that these metabolic hormones exert their antidiabetic effects through multiple molecular mechanisms. Accordingly, the current review aims to investigate key mechanisms and signaling pathways, such as the cAMP/PKA, Nrf2, PI3K/Akt, and AMPK pathways, associated with the antidiabetic effects of incretins. It also summarizes the outcomes of a group of clinical trials, which have evaluated the incretins' antidiabetic potential in diabetic patients.