Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: A time-course and dose-response study

Apiradee Sriwijitkamol, Dawn K. Coletta, Estela Wajcberg, Gabriela B. Balbontin, Sara M. Reyna, John Barrientes, Phyllis A. Eagan, Christopher P. Jenkinson, Eugenio Cersosimo, Ralph A. DeFronzo, Kei Sakamoto, Nicolas Musi

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

Abstract

Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI ∼25 kg/m2) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m2), 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)-1α, 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% VO2max) 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.

Original languageEnglish (US)
Pages (from-to)836-848
Number of pages13
JournalDiabetes
Volume56
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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