The effect of insulin and leptin on the regulation of the extracellular matrix and cell proliferation in glomerular mesangial cells (GMCs)

Abstract

Obesity is associated with the development of kidney damage. This may be a consequence of the direct effect of adipokines such as leptin, whose levels change in obesity or via the development of insulin-resistance. The latter results in hyperglycemia, which is a well established cause of nephropathy which manifests into end-stage renal disease. Nephropathy encompasses several structural alterations which are morphologically characterized by glomerular mesangial expansion, thickening of the glomerular basement membrane and the accumulation of extracellular matrix (ECM). For example, the synthesis of type IV collagen and fibronectin is enhanced in glomerular mesangial cells (GMC) under high glucose conditions and in the presence of the transforming growth factor-β1. (TGF-β1). However, it is unknown if leptin has a direct effect on GMC growth or ECM production. Furthermore, the effect of insulin on ECM production and regulation of insulin action by leptin in glomerular mesangial cells (GMC) remains to be established.