Integrin-linked kinase in muscle is necessary for the development of insulin resistance in diet-induced obese mice

Li Kang (Lead / Corresponding author), Shilpa Mokshagundam, Bradley Reuter, Daniel S. Lark, Claire C. Sneddon, Chandani Hennayake, Ashley S. Williams, Deanna P. Bracy, Freyja D. James, Ambra Pozzi, Roy Zent, David H. Wasserman

Research output: Contribution to journalArticle

16 Citations (Scopus)
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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 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 integrin-linked kinase (ILK), a key component of the IPP, in diet-induced muscle insulin resistance. Wildtype (ILKlox/lox) and muscle-specific ILK-deficient (ILKlox/loxHSAcre) mice were chow fed or high fat (HF) fed for 16wks. Body weight was not different between ILKlox/lox and ILKlox/loxHSAcre mice. However, HF-fed ILKlox/loxHSAcre mice had improved muscle insulin sensitivity relative to HF-fed ILKlox/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 ILKlox/loxHSAcre 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.
Original languageEnglish
Pages (from-to)1590-1600
Number of pages11
JournalDiabetes
Volume65
Issue number6
Early online date24 May 2016
DOIs
Publication statusPublished - 1 Jun 2016

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