Pleiotropic effects of glucagon-like peptide-1 (GLP-1)-based therapies on vascular complications in diabetes

Curr Pharm Des. 2011 Dec;17(38):4379-85. doi: 10.2174/138161211798999456.

Abstract

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, end-stage renal failure, acquired blindness and a variety of neuropathies, which could account for disabilities and high mortality rates in patients with diabetes. Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family. L cells in the small intestine secrete GLP-1 in response to food intake. GLP-1 not only enhances glucose-evoked insulin release from pancreatic β-cells, but also suppresses glucagon secretion from pancreatic α-cells. In addition, GLP-1 slows gastric emptying. Therefore, enhancement of GLP-1 secretion is a potential therapeutic target for the treatment of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) is a responsible enzyme that mainly degrades GLP-1, and the half-life of circulating GLP-1 is very short. Recently, DPP-4 inhibitors and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists have been developed and clinically used for the treatment of type 2 diabetes as a GLP-1-based medicine. GLP-1R is shown to exist in extra-pancreatic tissues such as vessels, kidney and heart, and could mediate the diverse biological actions of GLP-1 in a variety of tissues. So, in this paper, we review the pleiotropic effects of GLP-1-based therapies and its clinical utility in vascular complications in diabetes.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / metabolism
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / metabolism
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / metabolism
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Receptors, Glucagon / agonists*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon
  • Dipeptidyl Peptidase 4