Acute Effect of Human Recombinant Insulin-Like Growth Factor I on Renal Function in Humans

Abstract

We examined the acute effects of insulin-like growth factor I (IGF-I) on renal function in 8 normal subjects who received a 3-hour intravenous infusion of IGF-I at a rate of 0.4 μg/kg·min. After starting the IGF-I infusion, the plasma IGF-I concentration rose quickly and achieved a plateau after 90 min that was threefold above the basal value. During IGF-I infusion, progressive rises in glomerular filtration rate (from 93 ± 4 to 121 ± 6 ml/173 m²·min; p < 0.01) and renal plasma flow (from 529 ± 31 to 703 ± 55 ml/1.73 m²·min;p < 0.01) were observed, with no change in filtration fraction. The plasma levels of potassium and phosphate decreased significantly during the last 90 min of the study, while the plasma sodium concentration remained unchanged. A significant decrease in the fractional excretion of sodium, potassium, and phosphate was observed during the last 90 min of the IGF-I infusion period. The heart rate rose modestly with no change in mean arterial pressure. These findings show that, when administered acutely, IGF-I is a potent renal vasodilator, but is antinatriuretic. IGF-I also enhances potassium and phosphate uptake by extrarenal tissues and reduces renal potassium and phosphate excretion.

IGF-1 and insulin exert opposite actions on ClC-K2 activity in the cortical collecting ducts

“…It was proposed that IGF-1-induced inhibition of trans-epithelial Cl Ϫ absorption in the TAL would decrease oxygen consumption in the medullary TAL, thus contributing to a beneficiary role of IGF-1 during ischemia-reperfusion injury (29). However, intrarenal infusions of similar IGF-1 concentrations induce antidiuresis and antinatriuresis (4,6), which is consistent with augmented net NaCl reabsorption by renal tubule. Indeed, stimulatory effects of IGF-1 on sodium-transporting proteins, NKCC2 in the TAL and ENaC in CCD, are reported (3, 41).…”

“…In the CCD, insulin and IGF-1 stimulate ENaC-mediated sodium reabsorption through a PI3-K-dependent mechanism (41). Acute intravenous IGF-1 injection results in a significant reduction in the fractional Na ϩ excretion in humans (6). In patients with acromegaly, augmented circulating IGF-1 levels result in antinatriuresis and hypertension, which can be corrected with ENaC inhibitor amiloride (14,15).…”

Activation of PI3-Kinase Stimulates Endocytosis of ROMK via Akt1/SGK1-Dependent Phosphorylation of WNK1

“…In support of the idea that IGF1 inhibits renal K ϩ secretion in vivo, intravenous administration of IGF1 in humans decreases renal K ϩ excretion without significant changes in the filtered load of K ϩ . 26 Conversely, mice with liver-specific deletion of IGF1 have approximately 80% reduction in the circulating IGF1 and increased renal K ϩ excretion despite a normal filtered load of K ϩ . 27 Finally, inhibition of PI3K increases the density of native ROMK channels in mouse CCD, 28 providing further support for the physiologic role of PI3K in the inhibition of ROMK and renal K ϩ secretion.…”

Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II expression

“…Although the effect of GH/IGF-I on urinary potassium excretion is less well characterized than that on urinary sodium handling, decreased urinary excretion of potassium has previously been described during IGF-I treatment (Giordano & DeFronzo 1995), and GH treatment increases total body potassium content (Bengtsson et al 1993). In addition, increased renal IGF-I expression has been observed in potassium-depleted rats (Flyvberg et al 1992).…”