Low-protein diet suppresses serum insulin-like growth factor-1 and decelerates the progression of growth hormone-induced glomerulosclerosis

A low-protein (LP) diet has been associated with amelioration of renal func tion in glomerulosclerosis (GS). However, the mechanisms involved are still unclear. We have used a mouse transgenic for bovine growth hormone (GH), w hich develops progressive GS and exhibits consistently elevated levels of c irculating GH and insulin-like growth factor (IGF)-1, to study the effect o f dietary protein restriction. LP (6% protein) and normal-protein (NIF, 20% protein) diets were maintained for 30 weeks in mice with established GS of mild/moderate degree. The degree of GS was markedly attenuated in LP compa red to NP mice. Quantitative analysis revealed a significantly lower GS ind ex (1.4 +/- 0.9 in LP vs. 2.8 +/- 0.8 in NP) and glomerular volume (0.8 x 1 0(6) +/- 0.1 x 10(6) mum(3) in LP vs. 1.2 x 10(6) +/- 0.1 x 10(6) mum(3) in NP) in mice with restricted protein intake. These morphologic changes were accompanied by a significant reduction in renal expression of alpha (1) ty pe-IV collagen (2.4-fold) and tenascin (1.4-fold) in LP mice. Serum IGF-1 d ecreased by 40% and showed a significant correlation with a, type-IV collag en expression with the LP diet. The present finding supports the use of the LIP diet to decelerate the progression of GS and furthermore suggests that one of the mechanisms involved in this process is the GH/IGF-1 regulation by protein intake. Copyright (C) 2001 S. Karger AG, Basel.