Critical Role of Dipeptidyl Peptidase IV: A Therapeutic Target for Diabetes and Cancer

Mini Rev Med Chem. 2019;19(2):88-97. doi: 10.2174/1389557518666180423112154.

Abstract

Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.

Keywords: Dipeptidyl peptidase-IV; cancer; diabetes; diabetes mellitus; glucose homeostasis; peptide-1..

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Models, Molecular
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Signal Transduction / drug effects

Substances

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