Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study.
Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively. Twelve type 2 diabetic, eight obese, and eight lean subjects exercised on a cycle ergometer for 40 min. Muscle biopsies were done before, during, and after exercise. Subjects underwent this protocol on two occasions, at low (50% Vo(2max)) and moderate (70% Vo(2max)) intensities, with a 4-6 week interval. Exercise had no effect on LKB1 activity. Exercise had a time- and intensity-dependent effect to increase AMPK activity and AS160 phosphorylation. Obese and type 2 diabetic subjects had attenuated exercise-stimulated AMPK activity and AS160 phosphorylation. Type 2 diabetic subjects had reduced basal PGC-1 gene expression but normal exercise-induced increases in PGC-1 expression. Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects.
Sriwijitkamol
Apiradee
A
Texas Diabetes Institute, and Diabetes Division, University of Texas Health Science Center at San Antonio, TX 78207, USA.
Coletta
Dawn K
DK
Wajcberg
Estela
E
Balbontin
Gabriela B
GB
Reyna
Sara M
SM
Barrientes
John
J
Eagan
Phyllis A
PA
Jenkinson
Christopher P
CP
Cersosimo
Eugenio
E
DeFronzo
Ralph A
RA
Sakamoto
Kei
K
Musi
Nicolas
N
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D015444:Exercise / Q000502:physiology*; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D001786:Blood Glucose; D020690:GTPase-Activating Proteins; D009097:Multienzyme Complexes; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D009711:Nucleotides; C518767:TBC1D4 protein, human; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D006003:Glycogen; D000594:Amino Acid Oxidoreductases; C059460:1-aminocyclopropane-1-carboxylic acid oxidase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases