Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes

Front Endocrinol (Lausanne). 2022 Sep 20:13:984198. doi: 10.3389/fendo.2022.984198. eCollection 2022.

Abstract

Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet β-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied. The clinical application of VIP is limited because of its short half-life and wide distribution in the human body. Based on the binding properties of VIP and VPAC2 receptors, VPAC2-selective agonists have been developed to serve as novel hypoglycemic drugs. This review summarizes the physiological significance of VIP in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.

Keywords: VPAC2; VPAC2-selective agonists; glucose-dependence; insulin secretion; vasoactive intestinal peptide.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin Secretion
  • Receptors, Vasoactive Intestinal Peptide, Type II / agonists
  • Receptors, Vasoactive Intestinal Peptide, Type II / metabolism
  • Vasoactive Intestinal Peptide* / pharmacology
  • Vasoactive Intestinal Peptide* / therapeutic use

Substances

  • Hypoglycemic Agents
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Vasoactive Intestinal Peptide
  • Glucose