Insulin increases gelatinase activity in rat glomerular mesangial cells via ERK- and PI-3 kinase-dependent signalling

Diabetes, Obesity & Metabolism
Marian Pit-Siu Lee, Gary Sweeney

Abstract

Diabetic nephropathy is associated with increased accumulation of the extracellular matrix (ECM) in the kidney, which ultimately leads to kidney failure. This may occur due to excessive synthesis of ECM components or reduced degradation, a process primarily mediated by matrix metalloproteinases (MMPs). The direct effect of insulin on ECM synthesis and degradation in glomerular mesangial cells (GMCs) is unclear. Here, we show an increased gelatinase activity in conditioned media from insulin-treated rat GMCs, determined by gelatin zymography. Furthermore, we show using the specific inhibitors LY294002 and PD98059 that insulin induced increased gelatinase activity via an intracellular signalling mechanism involving phosphatidylinositol-3 kinase (PI-3K) and the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs) respectively. In addition, we demonstrate that PI-3 kinase and ERK1/2 MAPK are activated by insulin in GMCs. The appearance of protease activity at approximately 72 kDa suggested that MMP-2 activity may be induced by insulin, however, we did not detect an increase in MMP-2 expression by Western blotting. In summary, our results suggest that insulin can induce gelatinase activity in ...Continue Reading

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Citations

Jul 31, 2008·American Journal of Physiology. Endocrinology and Metabolism·Guenther BodenPeter Cheung
Nov 30, 2012·Clinical Science·Lorna J Hale, Richard J M Coward
Feb 13, 2020·Journal of Clinical Medicine·Nuria Garcia-FernandezMaría José Soler
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

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