Role of AMP-activated protein kinase in exercise capacity, whole body glucose homeostasis, and glucose transport in skeletal muscle. -Insight from analysis of a transgenic mouse model-

Nobuharu Fujii, Matthew M. Seifert, Erin M. Kane, Lauren E. Peter, Richard C. Ho, Schuyler Winstead, Michael F. Hirshman, Laurie J. Goodyear

Research output: Contribution to journalArticlepeer-review

Abstract

To examine the role of muscle AMP-activated protein kinase (AMPK) in maximal exercise capacity, whole body glucose homeostasis, and glucose transport in skeletal muscle, we generated muscle-specific transgenic mice carrying cDNAs of inactive AMPK α2 (α2i TG). Fed blood glucose was slightly higher in α2i TG mice compared to wild type littermates, however, the difference was not statistically significant. In α2i TG mice, glucose tolerance was slightly impaired in male, but not in female mice, compared to wild type littermates. Maximal exercise capacity was dramatically reduced in α2i TG mice, suggesting that AMPK α2 has a critical role in skeletal muscle during exercise. We confirmed that known insulin-independent stimuli of glucose transport including mitochondrial respiration inhibition, hyperosmolarity, and muscle contraction increased both AMPK α1 and α2 activities in isolated EDL muscle in wild type mice. While, α2 activation was severely blunted and α1 activation was only slightly reduced in α2i TG mice by these insulin independent stimuli compared to wild type mice. Mitochondrial respiration inhibition-induced glucose transport was fully inhibited in isolated EDL muscles in α2i TG mice. However, contraction- or hyperosmolarity-induced glucose transport was nearly normal. These results suggest that AMPK α2 activation is essential for some, but not all insulin-independent glucose transport.

Original languageEnglish (US)
Pages (from-to)S92-S98
JournalDiabetes Research and Clinical Practice
Volume77
Issue number3 SUPPL.
DOIs
StatePublished - Sep 2007

Keywords

  • AMP-activated protein kinase
  • Exercise capacity
  • Skeletal muscle

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Role of AMP-activated protein kinase in exercise capacity, whole body glucose homeostasis, and glucose transport in skeletal muscle. -Insight from analysis of a transgenic mouse model-'. Together they form a unique fingerprint.

Cite this