DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control

Arch Pharm Res. 2016 Aug;39(8):1114-28. doi: 10.1007/s12272-016-0813-x. Epub 2016 Aug 9.

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are an emerging class of antidiabetic drugs that constitutes approximately fifty percent of the market share of the oral hypoglycemic drugs. Its mechanism of action for lowering blood glucose is essentially via inhibition of the rapid degradation of incretin hormones, such as glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide (GIP), thus the plasma concentration of GLP-1 increases, which promotes insulin secretion from the pancreatic β cells and suppresses glucagon secretion from the α cells. In addition to the direct actions on the pancreas, GLP-1 exhibits diverse actions on different tissues through its action on GLP-1 receptor, which is expressed ubiquitously. Moreover, DPP-4 has multiple substrates besides GLP-1 and GIP, including cytokines, chemokines, neuropeptides, and growth factors, which are involved in many pathophysiological conditions. Recently, it was suggested that DPP-4 is a new adipokine secreted from the adipose tissue, which plays an important role in the regulation of the endocrine function in obesity-associated type 2 diabetes. Consequently, DPP-4 inhibitors have been reported to exhibit cytoprotective functions against various diabetic complications affecting the liver, heart, kidneys, retina, and neurons. This review outlines the current understanding of the effect of DPP-4 inhibitors on the complications associated with type 2 diabetes, such as liver steatosis and inflammation, dysfunction of the adipose tissue and pancreas, cardiovascular diseases, nephropathy, and neuropathy in preclinical and clinical studies.

Keywords: DPP-4 inhibitors; Diabetic complications; GLP-1; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Complications / blood
  • Diabetes Complications / drug therapy*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4