Person:
Holland, William

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Holland

First Name

William

Name

Holland, William

Filters

20081

Settings

Author's Publications: search.filters.isAuthorOfPublication.1449bcec-f97c-493d-b9a9-45cef2d09e07

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    Publication
    Ablation of AMP-Activated Protein Kinase \(\alpha\)2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice
    (American Diabetes Association, 2008) Fujii, Nobuharu; Ho, Richard C.; Manabe, Yasuko; Jessen, Niels; Toyoda, Taro; Holland, William; Summers, Scott A.; Hirshman, Michael F.; Goodyear, Laurie
    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 \(\alpha\)2 catalytic subunit (\(\alpha\)2i 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 \(\alpha\)2i 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 \(\mu\)U/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by \(\sim\)50% in \(\alpha\)2i 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 \(\alpha\)2i TG mice. High-fat feeding in \(\alpha\)2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. Conclusions: The lack of skeletal muscle AMPK \(\alpha\)2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK \(\alpha\)2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.