Integrin-Linked Kinase Is Necessary for the Development of Diet-Induced Hepatic Insulin Resistance
Year: 2016
Type: article
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 ILKlox/lox mice were crossed with Albcre mice to produce a hepatocyte-specific ILK deletion (ILKlox/loxAlbcre). 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.
Source: Diabetes
DOI: 10.2337/db16-0484
Institutions: Vanderbilt University, Nashville VA Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G120444612, Betal Integrin and Renal Tubulogenesis, G1751646407, G18496906, G2019238319, G2304076072, G2532530556, G311862290, G318902089, Structure Function Analysis of Integrins alpha1beta1 and alpha2beta2, Vanderbilt O'Brien Kidney Center, G3989539122, Vanderbilt Mouse Metabolic Phenotyping Center, G48094425, Integrin/TGF-beta Axis in Tubulointerstitial Fibrosis, Exercise and Fuel Metabolism, G711058138, G712063428, G8355878738, Diabetes Research and Training Center, G8483227103, Vanderbilt Diabetes Research Center, G904814646
OpenAlex ID: W2558947320