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Publication
Integrin-Linked Kinase in Muscle Is Necessary for the Development of Insulin
Resistance in Diet-Induced Obese Mice.
Authors Kang L, Mokshagundam S, Reuter B, Lark DS, Sneddon CC, Hennayake C, Williams AS,
Bracy DP, James FD, Pozzi A, Zent R, Wasserman DH
Submitted By Submitted Externally on 10/26/2016
Status Published
Journal Diabetes
Year 2016
Date Published 6/1/2016
Volume : Pages 65 : 1590 - 600
PubMed Reference 27207548
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, a2ß1. 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 ß-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.








Genes
SymbolDescription
Acta1actin, alpha 1, skeletal muscle
Ilkintegrin linked kinase

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