Ablation of AMP-activated protein kinase α 2 activity exacerbates insulin resistance induced by high-fat feeding of mice

Nobuharu Fujii, Richard C. Ho, Yasuko Manabe, Niels Jessen, Taro Toyoda, William L. Holland, Scott A. Summers, Michael F. Hirshman, Laurie J. Goodyear

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE-We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. RESEARCH DESIGN AND METHODS-Muscle-specific transgenic mice expressing an inactive form of the AMPK α2 catalytic subunit (α2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. RESULTS-Compared with wild-type mice, glucose tolerance in α2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 (μU/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by - 50% in α2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the α2i TG mice. High-fat feeding in α2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. CONCLUSIONS-The lack of skeletal muscle AMPK α2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK α2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.

Original languageEnglish (US)
Pages (from-to)2958-2966
Number of pages9
JournalDiabetes
Volume57
Issue number11
DOIs
StatePublished - Nov 2008

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AMP-Activated Protein Kinases
Insulin Resistance
Fats
Skeletal Muscle
Insulin
Glucose
Glucose Intolerance
Diet
Muscles
Metformin
High Fat Diet
Transgenic Mice
Life Style
Catalytic Domain
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fujii, N., Ho, R. C., Manabe, Y., Jessen, N., Toyoda, T., Holland, W. L., ... Goodyear, L. J. (2008). Ablation of AMP-activated protein kinase α 2 activity exacerbates insulin resistance induced by high-fat feeding of mice. Diabetes, 57(11), 2958-2966. https://doi.org/10.2337/db07-1187

Ablation of AMP-activated protein kinase α 2 activity exacerbates insulin resistance induced by high-fat feeding of mice. / Fujii, Nobuharu; Ho, Richard C.; Manabe, Yasuko; Jessen, Niels; Toyoda, Taro; Holland, William L.; Summers, Scott A.; Hirshman, Michael F.; Goodyear, Laurie J.

In: Diabetes, Vol. 57, No. 11, 11.2008, p. 2958-2966.

Research output: Contribution to journalArticle

Fujii, N, Ho, RC, Manabe, Y, Jessen, N, Toyoda, T, Holland, WL, Summers, SA, Hirshman, MF & Goodyear, LJ 2008, 'Ablation of AMP-activated protein kinase α 2 activity exacerbates insulin resistance induced by high-fat feeding of mice', Diabetes, vol. 57, no. 11, pp. 2958-2966. https://doi.org/10.2337/db07-1187
Fujii, Nobuharu ; Ho, Richard C. ; Manabe, Yasuko ; Jessen, Niels ; Toyoda, Taro ; Holland, William L. ; Summers, Scott A. ; Hirshman, Michael F. ; Goodyear, Laurie J. / Ablation of AMP-activated protein kinase α 2 activity exacerbates insulin resistance induced by high-fat feeding of mice. In: Diabetes. 2008 ; Vol. 57, No. 11. pp. 2958-2966.
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AU - Toyoda, Taro

AU - Holland, William L.

AU - Summers, Scott A.

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