Ashley Williams
Last active: 3/13/2015


The prevalence of Type 2 diabetes has increased dramatically in recent years due to excess dietary fat and sedentary lifestyles.  High fat (HF) feeding is associated with hepatic insulin resistance, increased hepatic triglyceride (TG) accumulation and excess accumulation of extracellular matrix (ECM) proteins.  The nature of these associations and whether they are mechanistically linked in the HF fed state remains to be resolved. 

The ECM is composed of a diverse array of proteins including collagens, proteoglycans, and laminins.  Integrins are cell surface receptors that interact with the ECM to facilitate inside-out and outside-in cell signaling.  The two main collagen binding receptors are integrins α1β1 and α2β1.  Recent studies from our laboratory demonstrate that deletion of integrin α1β1, but not integrin α2β1, leads to further impairments in hepatic insulin resistance, suggesting that integrin α1β1 is protective against hepatic insulin resistance.  Integrins facilitate crosstalk between the ECM and intracellular signaling pathways; therefore, it is reasonable to speculate that changes in extracellular events are linked to defects in hepatic insulin action.  The aims of my dissertation are designed to determine the role of the ECM in diet induced hepatic insulin resistance. 


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Featured publications are shown below:

  1. Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance. Williams AS, Kang L, Zheng J, Grueter C, Bracy DP, James FD, Pozzi A, Wasserman DH (2015) J Biol Chem 290(10): 6546-57
    › Citation · 25593319 (PubMed) · PMC4358288 (PubMed Central)