Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat

Abstract

An increase in plasma insulin-like growth factor I (IGF-I) levels by growth hormone injection or IGF-I infusion can raise renal plasma flow and glomerular filtration rate. However, it is not known whether a more physiological stimulus for IGF-I will also increase IGF-I in the kidney and whether the increase in renal or serum IGF-I is correlated with the increase in renal plasma flow and glomerular filtration rate. Male rats were pair fed either a high-protein (36% protein, N = 9) or a low-protein but isocaloric diet (9% protein, N = 9) for 10 to 14 days. Renal plasma flow and glomerular filtration rate were then estimated by clearance measurements, and IGF-I was measured in extracted serum, liver, renal cortical tissue, and glomeruli. Body weight gain and combined kidney weight were higher in high-protein rats as compared with low-protein animals (0.86 ± 0.02 SEM versus 0.77 ± 0.02 g/100 g body wt; P < 0.05), but liver weights were not different. Serum, liver, and glomerular IGF-I levels were also higher in the high-protein rats as compared with the low-protein animals (serum, 1.12 ± 0.03 versus 0.80 ± 0.06 U/mL, P < 0.05; liver, 183 ± 17 versus 117 ± 16 mU/g wet wt, P < 0.05; glomeruli, 7.43 ± 0.73 versus 4.81 ± 0.59 mU/mg of protein, P < 0.05). In contrast, the renal cortical IGF-I levels were not different in high-protein versus low-protein rats. Renal plasma flow and glomerular filtration rate were higher and renal vascular resistance and filtration fraction were lower (P < 0.05) in the high-protein versus the low-protein rats. The glomerular filtration rate correlated positively with the serum IGF-I concentration (r= 0.666; P < 0.02). Glomerular filtration rate, when adjusted for renal hypertrophy (i.e., expressed as mL/min/g of kidney weight), also correlated with glomerular IGF-I concentration (r = 0.819; P < 0.01). We conclude that IGF-I is increased in serum, liver, and glomeruli during a physiological stimulus (i.e., high-protein diet feeding) that causes renal hypertrophy and increased renal hemodynamics. The rise in IGF-I may be a cause of renal hypertrophy and hyperfiltration that occurs with high-protein diets.