Glycogen synthase kinase 3beta as a target for the therapy of shock and inflammation

Shock. 2007 Feb;27(2):113-23. doi: 10.1097/01.shk.0000238059.23837.68.


After the discovery that glycogen synthase kinase (GSK) 3beta plays a fundamental role in the regulation of the activity of nuclear factor kappaB, a number of studies have investigated the effects of this protein kinase in the regulation of the inflammatory process. The GSK-3beta inhibition, using genetically modified cells and chemically different pharmacological inhibitors, affects the regulation of various inflammatory mediators in vitro and in vivo. Insulin, an endogenous inhibitor of GSK-3 in the pathway leading to the regulation of glycogen synthase activity, has recently been clinically used in the therapy for septic shock. The beneficial anti-inflammatory effects of insulin in preclinical and clinical studies could possibly be due, at least in part, to the inhibition of GSK-3 and not directly correlated to the regulation of blood glucose. We describe the latest studies describing the effects of GSK-3 inhibition as potential target of the therapy for diseases associated with inflammation, ischemia/reperfusion, and shock.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Blood Glucose / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Glycogen Synthase / metabolism*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / enzymology
  • Insulin / therapeutic use
  • NF-kappa B / metabolism*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / enzymology
  • Shock / drug therapy
  • Shock / enzymology*


  • Anti-Inflammatory Agents
  • Blood Glucose
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • NF-kappa B
  • Glycogen Synthase
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3