Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice.

 

Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice.

Show full item record

Title: Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice.
Author: Fujii, Nobuharu; Ho, Richard C; Manabe, Yasuko; Jessen, Niels; Toyoda, Taro; Holland, William L; Summers, Scott A; Hirshman, Michael F; Goodyear, Laurie J
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 alpha2 catalytic subunit (alpha2i 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 alpha2i 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 microU/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by approximately 50% in alpha2i 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 alpha2i TG mice. High-fat feeding in alpha2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. CONCLUSIONS: The lack of skeletal muscle AMPK alpha2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK alpha2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.
Citation: Diabetes. 2008 Nov;57(11): 2958-66. EPub 2008 Aug 26
PMC: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18728234

This item appears in the following Collection(s)

Show full item record