Skip to main content

Integrin-Linked Kinase Is Necessary for the Development of Diet-Induced Hepatic Insulin Resistance.

Citation
Williams, A. S., et al. “Integrin-Linked Kinase Is Necessary For The Development Of Diet-Induced Hepatic Insulin Resistance.”. Diabetes, pp. 325-334.
Center Vanderbilt University
Author Ashley S Williams, Elijah Trefts, Louise Lantier, Carrie A Grueter, Deanna P Bracy, Freyja D James, Ambra Pozzi, Roy Zent, David H Wasserman
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 mice were crossed with Albcre mice to produce a hepatocyte-specific ILK deletion (ILKAlbcre). 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.

Year of Publication
2017
Journal
Diabetes
Volume
66
Issue
2
Number of Pages
325-334
Date Published
12/2017
ISSN Number
1939-327X
DOI
10.2337/db16-0484
Alternate Journal
Diabetes
PMID
27899483
PMCID
PMC5248997
Download citation