Tissue-specificity of insulin action and resistance*

Abstract

Insulin resistance is the most important pathophysiological feature in many pre-diabetic states. Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion by pancreatic beta cells. The creation of monogenic or polygenic genetically manipulated mice models in a tissue-specific manner was of great help to elucidate the tissue-specificity of insulin action and its contribution to the overall insulin resistance. However, complete understanding of the molecular bases of the insulin action and resistance requires the identification of the intracellular pathways that regulate insulin-stimulated proliferation, differentiation and metabolism. Accordingly, cell lines derived from insulin target tissues such as brown adipose tissue, liver and beta islets lacking insulin receptors or sensitive candidate genes such as IRS-1, IRS-2, IRS-3, IR and PTP1B were developed. Indeed, these cell lines have been also very useful to understand the tissue-specificity of insulin action and inaction.

Key words::

• insulin signalling
• insulin receptor substrates
• tissue-specificity
• insulin resistance genes
• insulin resistance
• mouse models
• cellular models

Acknowledgments

This work was supported by Grants SAF2004/5545, SAF2005/0014, SAF2007/60058 and SAF2008/00031. CIBER de Diabetes y Enfermedades Metabólicas Asociadas is an ISCIII project. The author gives special thanks to Dr. M.A. Valverde for her invaluable scientific contribution to this review. The author declares no conflict of interests.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.