Novel factors as therapeutic targets to treat diabetes. Focus on leptin and ghrelin

Expert Opin Ther Targets. 2009 May;13(5):583-91. doi: 10.1517/14728220902914834.

Abstract

Background: Obesity is the major cause of type 2 diabetes. In the mid 1990s interest in adipose tissue was revived by the discovery of leptin. The association of obesity and diabetes emphasizes their shared physiopathological features. At the end of the 1990s, ghrelin, a potent gastric orexigenic factor, was found to be involved in obesity. Leptin and ghrelin have opposite actions in several tissues including the regulation of feeding in the brain.

Objective/methods: To survey the role of leptin and ghrelin in glucose metabolism. We summarize the current state of research and discuss the roles of ghrelin and leptin in glucose homeostases and the potential application of drugs targeting leptin and ghrelin signalling to prevent and treat diabetes.

Results/conclusions: A pressing challenge is to determine how leptin, ghrelin and other adipokines or gastric factors are involved in metabolic disorders. Answering these questions will require the development of new pharmacological tools that target specific adipokine systems. Hopefully, new therapeutic targets will be identified.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Child
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Delivery Systems*
  • Drug Evaluation, Preclinical
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Female
  • Ghrelin / antagonists & inhibitors*
  • Ghrelin / physiology
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance / physiology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Leptin / agonists*
  • Leptin / deficiency
  • Leptin / physiology
  • Leptin / therapeutic use
  • Mice
  • Mice, Knockout
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / physiopathology
  • Receptors, Ghrelin / drug effects
  • Receptors, Ghrelin / physiology
  • Receptors, Leptin / drug effects
  • Receptors, Leptin / physiology

Substances

  • Ghrelin
  • Hypoglycemic Agents
  • Leptin
  • Receptors, Ghrelin
  • Receptors, Leptin
  • Glucose