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Publication
Integrin-Linked Kinase Is Necessary for the Development of Diet-Induced Hepatic
Insulin Resistance.
Authors Williams AS, Trefts E, Lantier L, Grueter CA, Bracy DP, James FD, Pozzi A, Zent
R, Wasserman DH
Submitted By Submitted Externally on 2/6/2017
Status Published
Journal Diabetes
Year 2017
Date Published
Volume : Pages 66 : 325 - 334
PubMed Reference 27899483
Abstract The liver extracellular matrix (ECM) expands with high-fat (HF) feeding. This
finding led us to address whether receptors for the ECM, integrins, are key to
the development of diet-induced hepatic insulin resistance. Integrin-linked
kinase (ILK) is a downstream integrin signaling molecule involved in multiple
hepatic processes, including those related to differentiation, wound healing,
and metabolism. We tested the hypothesis that deletion of ILK in mice on an HF
diet would disrupt the ECM-integrin signaling axis, thereby preventing the
transformation into the insulin-resistant liver. To determine the role of ILK in
hepatic insulin action in vivo, male C57BL/6J ILK(lox/lox) mice were crossed
with Albcre mice to produce a hepatocyte-specific ILK deletion
(ILK(lox/lox)Albcre). Results from this study show that hepatic ILK deletion has
no effect on insulin action in lean mice but sensitizes the liver to insulin
during the challenge of HF feeding. This effect corresponds to changes in the
expression and activation of key insulin signaling pathways as well as a greater
capacity for hepatic mitochondrial glucose oxidation. This demonstrates that ILK
contributes to hepatic insulin resistance and highlights the previously
undefined role of integrin signaling in the pathogenesis of diet-induced hepatic
insulin resistance.




Strains
StrainDevelopment StatusCreation MethodOptions
B6N;129-Ilktm1Star/JPhenotyping ongoingknockin
View
B6.129-Ilktm1Star Tg(Alb-cre)21MgnPhenotyping ongoingknockout
View




Genes
SymbolDescription
Ilkintegrin linked kinase
Albalbumin

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