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1 Department of Zoology, Brigham Young University, Provo, Utah 84602; and 2 Department of Biochemistry, The University, Dundee DD1 5EH, Scotland, United Kingdom
Adenosine 5'-monophosphate-activated protein kinase (AMPK)
now appears to be a metabolic master switch, phosphorylating key target
proteins that control flux through metabolic pathways of hepatic
ketogenesis, cholesterol synthesis, lipogenesis, and triglyceride synthesis, adipocyte lipolysis, and skeletal muscle fatty acid oxidation. Recent evidence also implicates AMPK as being responsible for mediating the stimulation of glucose uptake induced by muscle contraction. In addition, the secretion of insulin by insulin secreting
(INS-1) cells in culture is modulated by AMPK activation. The net
effect of AMPK activation is stimulation of hepatic fatty acid
oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid
oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic 
-cells. In skeletal muscle, AMPK is
activated by contraction. Type 2 diabetes mellitus is likely to be a
disease of numerous etiologies. However, defects or disuse (due to a
sedentary lifestyle) of the AMPK signaling system would be predicted to result in many of the metabolic perturbations observed in Type 2 diabetes mellitus. Increased recruitment of the AMPK signaling system,
either by exercise or pharmaceutical activators, may be effective in
correcting insulin resistance in patients with forms of impaired
glucose tolerance and Type 2 diabetes resulting from defects in the
insulin signaling cascade.
adenosine 5'-monophosphate-activated protein kinase kinase; fatty acid oxidation; glucose uptake; GLUT-4; insulin insensitivity; malonylcoenzyme A
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