Targeting the AMPK pathway for the treatment of Type 2 diabetes.
Type 2 diabetes is one of the fastest growing public health problems worldwide, resulting from both genetic factors and inadequate adaptation to environmental changes. It is characterized by abnormal glucose and lipid metabolism due in part to resistance to the actions of insulin in skeletal muscle, liver and fat. AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, acts as an integrator of regulatory signals monitoring systemic and cellular energy status. The growing realization that AMPK regulates the coordination of anabolic and catabolic metabolic processes represents an attractive concept for type 2 diabetes therapy. Recent findings showing that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile and blood pressure in insulin-resistant rodents suggest that this kinase could be a novel therapeutic target in the treatment of type 2 diabetes. Consistent with these results, physical exercise and major classes of antidiabetic drugs have recently been reported to activate AMPK. In the present review, we update these topics and discuss the concept of targeting the AMPK pathway for the treatment of type 2 diabetes.
Viollet
Benoit
B
Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Department Endocrinology, Metabolism and Cancer, Paris, France.
Lantier
Louise
L
Devin-Leclerc
Jocelyne
J
Hebrard
Sophie
S
Amouyal
Chloe
C
Mounier
Remi
R
Foretz
Marc
M
Andreelli
Fabrizio
F
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000628:therapy*; D004789:Enzyme Activation; D015444:Exercise; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology; D050356:Lipid Metabolism; D011487:Protein Conformation
D055372:AMP-Activated Protein Kinases; D005947:Glucose