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- Title
Integrin-Linked Kinase in Muscle Is Necessary for the Development of Insulin Resistance in Diet-Induced Obese Mice.
- Authors
Li Kang; Mokshagundam, Shilpa; Reuter, Bradley; Lark, Daniel S.; Sneddon, Claire C.; Hennayake, Chandani; Williams, Ashley S.; Bracy, Deanna P.; James, Freyja D.; Pozzi, Ambra; Zent, Roy; Wasserman, David H.; Kang, Li
- Abstract
Diet-induced muscle insulin resistance is associated with expansion of extracellular matrix (ECM) components, such as collagens, and the expression of collagen-binding integrin, α2β1. Integrins transduce signals from ECM via their cytoplasmic domains, which bind to intracellular integrin-binding proteins. The integrin-linked kinase (ILK)-PINCH-parvin (IPP) complex interacts with the cytoplasmic domain of β-integrin subunits and is critical for integrin signaling. In this study we defined the role of ILK, a key component of the IPP complex, in diet-induced muscle insulin resistance. Wild-type (ILK(lox/lox)) and muscle-specific ILK-deficient (ILK(lox/lox)HSAcre) mice were fed chow or a high-fat (HF) diet for 16 weeks. Body weight was not different between ILK(lox/lox) and ILK(lox/lox)HSAcre mice. However, HF-fed ILK(lox/lox)HSAcre mice had improved muscle insulin sensitivity relative to HF-fed ILK(lox/lox) mice, as shown by increased rates of glucose infusion, glucose disappearance, and muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. Improved muscle insulin action in the HF-fed ILK(lox/lox)HSAcre mice was associated with increased insulin-stimulated phosphorylation of Akt and increased muscle capillarization. These results suggest that ILK expression in muscle is a critical component of diet-induced insulin resistance, which possibly acts by impairing insulin signaling and insulin perfusion through capillaries.
- Subjects
INTEGRINS; INSULIN resistance; COLLAGEN; INTEGRIN-linked kinase; PHOSPHORYLATION; TREATMENT of diabetes; GLUCOSE metabolism; ANIMAL experimentation; ANIMALS; CELLULAR signal transduction; DIET; EXTRACELLULAR space; INSULIN; MICE; OBESITY; RESEARCH funding; TRANSFERASES; SKELETAL muscle; GLUCOSE clamp technique
- Publication
Diabetes, 2016, Vol 65, Issue 6, p1590
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-1434