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Título:	IRS2 is an essential molecule for insulin signalling in renal cells
Autor:	Santamaria, Beatriz CSIC ORCID; González-Rodríguez, Águeda CSIC ORCID; Coward, R. J.; Valverde, Ángela M. CSIC ORCID
Fecha de publicación:	2012
Citación:	EASD 2012
Resumen:	[Background and aims]: Diabetic nephropathy is the commonest cause of end-stage renal failure in the world. Its natural history is dominated by progressive albuminuria. Recently it has been demonstrated that podocyte insulin resistance may be implicated in this diabetic complication. Podocytes are crucial in maintaining integrity of the glomerular filtration barrier and preventing albuminuria. On this basis, we investigated the role of the IRS 2 in the development of diabetic nephropathy and specifically if IRS 2 affects insulin signalling in kidney function. [Materials and methods]: We have used an in vivo and in vitro approach to study the role of IRS2 in the podocyte of the glomerulus. Initially we studied the renal phenotype of whole body IRS2 deficient mice. We then generated conditionally immortalised murine podocyte celllines from these mice using a temperature sensitive SV 40 large T antigen construct to study its role in insuÍin signalling in this cell. [Results]: IRS2-deficient (IRS2-/-) animals present defects in both insulin action and insulin production. By 12 weeks of age, a proportion of IRS2-/- mice are diabetic and, therefore, they exhibit a severe hyperglycemia (glucose levels >400 mg/dl) and develop significan\ levels of albuminuria. They exhibit mild glomerular abnormalities (matrix accumulation) using light microscopy and have podocyte abnormalities using electron microscopy with significant foot process widening. Fascinatingly the immortalised cells from these mice are profoundly insulin resistant in comparison to podocytes derived from agematched wild-type mouse controls (insulin-stimulated increase in glucose uptake 150% WT vs 100% IRS2 KO). They also have significantly impaired AKT (45 % PKB) signalling in response to insulin and exhibit impaired GLUT4 membrane translocation. They have comparable levels of IRS1 in comparison to controls. [Conclusion]: These results show suggest the critical importance of IRS2 in maintaining glomerular function in glomeruli being critica! for normal kidney function. Furthermore, the in vitro studies demonstrate that IRS2 is a critical node for insulin signalling in the podocytes.
Descripción:	Resumen del póster presentado al 48th European Association for the Study of Diabetes (EASD) Annual Meeting, celebrado en Berlin (Alemania) del 1 al 5 de octubre de 2012.-- et al.
URI:	http://hdl.handle.net/10261/154293
Aparece en las colecciones:	(IIBM) Comunicaciones congresos