AMP-activated protein kinase α2 activity is not essential for contraction-and hyperosmolarity-induced glucose transport in skeletal muscle

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

Research output: Contribution to journalArticlepeer-review

Abstract

To examine the role of AMP-activated protein kinase (AMPK) in muscle glucose transport, we generated muscle-specific transgenic mice (TG) carrying cDNAs of inactive α2 (α2i TG) and α1 (α1i TG) catalytic subunits. Extensor digitorum longus (EDL) muscles from wild type and TG mice were isolated and subjected to a series of in vitro incubation experiments. In α2i TG mice basal α2 activity was barely detectable, whereas basal α1 activity was only partially reduced. Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK α2 activity in α2i TG mice, whereas α1 activation was attenuated by only 30-50%. Glucose transport was measured in vitro using isolated EDL muscles from α2i TG mice. AICAR- and rotenone-stimulated glucose transport was fully inhibited in α2i TG mice; however, the lack of AMPK α2 activity had no effect on contraction-or sorbitol-induced glucose transport. Similar to these observations in vitro, contraction-stimulated glucose transport, assessed in vivo by 2-deoxy-D-[3H]glucose incorporation into EDL, tibialis anterior, and gastrocnemius muscles, was normal in α2i TG mice. Thus, AMPK α2 activation is essential for some, but not all, insulin-independent glucose transport. Muscle contraction- and hyperosmolarity-induced glucose transport may be regulated by a redundant mechanism in which AMPK α2 is one of multiple signaling pathways.

Original languageEnglish (US)
Pages (from-to)39033-39041
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number47
DOIs
StatePublished - Nov 25 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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