Implication of IGF-1 in other renal pathologies The beneficial effects of IGF-1 treatment have also been observed in rats with acute renal tubulointerstitial injury induced by ureteral obstruction.50 Likewise, in vivo studies in this mouse model of obstructive nephropathy have demonstrated that IGF-1 administration reduces apoptosis, an effect that was abolished by inhibition of the ERK/MAPK signaling pathway.51 Of particular interest, renal hypertrophy in diabetes is also associated with elevated kidney IGF-1 production, similar to the compensatory hypertrophy observed in the contralateral kidney following Uni-Nx.52 In fact, while rats subjected to Uni-Nx show increased size of the remnant kidney by 30%, animals undergoing streptozotocin-induced diabetes show a 32% increase in renal size, reaching a 46% increase when the diabetic rats were subjects to Uni-Nx, which was consistent with the increased kidney IGF-1 expression.53 These effects of IGF-1 on compensatory renal growth are reduced by administration of an IGF1R antagonism in both, diabetic and Uni-Nx rats,54 as well as ex-vivo compensatory hyperfiltration in kidney samples from Uni-Nx rats.55 Similar results have been observed in non-obese diabetic mice treated with an antagonist of the GH receptor.56 These studies demonstrate that diabetes is an inductor of renal hypertrophy through activation of the kidney IGF-1 levels
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J Clin Oncol 2006;24:1761-9
