Possible Mechanisms and Molecular Signaling of Incretins against the Development of Type 2 Diabetes Mellitus

Curr Mol Pharmacol. 2023;16(4):448-464. doi: 10.2174/1874467215666220829102020.

Abstract

The increasing number of cases of diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gutderived 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 evaluating the incretins' antidiabetic potential in diabetic patients.

Keywords: Diabetes mellitus; agonist; blood glucose levels; incretins; molecular mechanisms; signaling pathways.

Publication types

  • Review

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Incretins / metabolism
  • Incretins / therapeutic use
  • Insulin / metabolism
  • Phosphatidylinositol 3-Kinases

Substances

  • Incretins
  • Blood Glucose
  • Phosphatidylinositol 3-Kinases
  • Hypoglycemic Agents
  • Insulin
  • Dipeptidyl-Peptidase IV Inhibitors