AMP-activated protein kinase activators in diabetic ulcers: from animal studies to Phase II drugs under investigation

Expert Opin Investig Drugs. 2014 Sep;23(9):1253-65. doi: 10.1517/13543784.2014.922951. Epub 2014 May 26.

Abstract

Introduction: Diagnosed cases of diabetes have gradually increased year by year, and research on diabetes mellitus (DM) has attracted greater attention from the medical profession. Diabetic ulcers present persistent pain and the risk of bacterial infection. However, no promising treatment methods have been found. As a regulator of cellular energy balance, 5' adenosine monophosphate-activated protein kinase (AMPK) has been suggested as a drug target for DM, including such drugs as metformin.

Areas covered: This review summarizes the current research and clinical trials of AMPK activators on diabetic wound healing and diabetic ulcers. Furthermore, it discusses the feasibility of AMPK activators in the treatment of diabetic wounds.

Expert opinion: Animal studies have demonstrated that AMPK activators are a potential treatment for diabetic ulcers. AMPK activators alleviate tissue inflammation and promote re-epithelialization in diabetic wounds. However, due to the complicated pathological mechanism of diabetic foot ulcers, AMPK activators should be combined with other approaches. The new strategies for combination therapy with AMPK activator may provide a therapeutic advantage for patients with diabetic ulcers.

Keywords: AMP-activated protein kinase; diabetes mellitus; diabetic ulcer; metformin; wound healing.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / drug effects*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Clinical Trials, Phase II as Topic
  • Diabetic Foot / drug therapy*
  • Diabetic Foot / enzymology
  • Diabetic Foot / pathology
  • Drug Design
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Molecular Targeted Therapy
  • Wound Healing / drug effects*

Substances

  • Hypoglycemic Agents
  • Metformin
  • AMP-Activated Protein Kinases