Targeted therapies of the LKB1/AMPK pathway for the treatment of insulin resistance

Future Med Chem. 2010 Dec;2(12):1785-96. doi: 10.4155/fmc.10.264.

Abstract

Type II diabetes is characterized by elevated serum glucose levels and altered lipid metabolism due to peripheral insulin resistance and defects of insulin secretion in the pancreatic β-cells. While some cases of obesity and Type II diabetes result from genetic dysfunction, the increased worldwide incidence of these two disorders strongly suggest that the contribution of environmental factors such as sedentary lifestyles and high-calorie intake may disrupt energy balance. AMP-activated protein kinase and its upstream kinase liver kinase B1 are conserved serine/threonine kinases regulating anabolic and catabolic metabolic processes, therefore representing attractive therapeutic targets for the treatment of obesity and Type II diabetes. In this review, we will discuss the advantages of targeting the liver kinase B1/AMP-activated protein kinase pathway for the treatment of metabolic diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Discovery
  • Humans
  • Insulin Resistance*
  • Liver / drug effects
  • Liver / enzymology*
  • Metabolic Diseases / drug therapy*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction / drug effects

Substances

  • STK11 protein, human
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases