AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes.
Acute or chronic activation of AMP-activated protein kinase (AMPK) increases insulin sensitivity. Conversely, reduced expression and/or function of AMPK might play a role in insulin resistance in type 2 diabetes. Thus protein expression of the seven subunit isoforms of AMPK and activities and/or phosphorylation of AMPK and acetyl-CoA carboxylase-beta (ACCbeta) was measured in skeletal muscle from obese type 2 diabetic and well-matched control subjects during euglycemic-hyperinsulinemic clamps. Protein expression of all AMPK subunit isoforms (alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3) in muscle of obese type 2 diabetic subjects was similar to that of control subjects. In addition, alpha1- and alpha2-associated activities of AMPK, phosphorylation of alpha-AMPK subunits at Thr172, and phosphorylation of ACCbeta at Ser221 showed no difference between the two groups and were not regulated by physiological concentrations of insulin. These data suggest that impaired insulin action on glycogen synthesis and lipid oxidation in skeletal muscle of obese type 2 diabetic subjects is unlikely to involve changes in AMPK expression and activity.
Højlund
Kurt
K
Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Mustard
Kirsty J
KJ
Staehr
Peter
P
Hardie
D Grahame
DG
Beck-Nielsen
Henning
H
Richter
Erik A
EA
Wojtaszewski
Jørgen F P
JF
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D015309:Glucose Clamp Technique; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D009765:Obesity / Q000150:complications* / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D007527:Isoenzymes; D009097:Multienzyme Complexes; C526181:PRKAA2 protein, human; C526182:PRKAB1 protein, human; C526183:PRKAB2 protein, human; C526222:PRKAG1 protein, human; C526225:PRKAG3 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000103:Acetyl-CoA Carboxylase