Abstract / Summary
Abstract Integrins are a superfamily of heterodimeric cell surface receptors which interact with the extracellular environment and play essential roles in cell adhesion, motility, cell–cell interactions and intracellular signalling. Remodelling of the extracellular matrix has been implicated in insulin resistance; however, questions remain over the extent to which alterations in integrin-binding domains in extracellular proteins, or in the abundance of integrins themselves, contribute to metabolic homeostasis and metabolic disorders. In this review, we critically assess integrins as potential mediators of metabolic dysfunction and as putative targets for metabolic disease. We describe the current understanding of the complex roles of integrins in insulin signalling and metabolic diseases arising from in vivo and in vitro studies. We discuss the evidence supporting roles in metabolic regulation for each integrin subfamily and for their downstream signalling targets focal adhesion kinase and integrin-linked kinase. We highlight the genetic knockout or knockdown studies demonstrating that specific integrins are essential for metabolic homeostasis. The integrin β 1 subunit receives particular attention due to its role in forming multiple integrin heterodimers and data demonstrating an essential role in modulating insulin signalling. We highlight where further research is needed to determine the extent to which altered integrin abundance or signalling contribute to metabolic physiology or disease. Finally, we discuss the potential for integrins to be exploited as putative therapeutic targets and speculate on whether the development of integrin-targeting drugs pursued in other therapy areas could be extended to generate novel treatment for metabolic disease.