AJP - Renal Physiology, Vol 271, Issue 2 440-F445, Copyright © 1996 by American Physiological Society

ARTICLES

Insulin-like growth factor-I action on glucose transport in acute renal failure

R. H. Mak and O. Mehls
Department of Pediatrics, Stanford University School of Medicine, California 94305-5119, USA.

Insulin resistance is common in acute renal failure (ARF). Insulin-like growth factor (IGF)-I has insulin-like actions. The present study was undertaken to determine whether effects of IGF-I on glucose transport are maintained in rats with ARF and to compare these actions of IGF-I with those of insulin. ARF was induced in male Sprague-Dawley rats by bilateral ureteric ligation, and vascular catheters were inserted at the same time in all animals. Sham-operated controls were pair fed, and metabolic studies were performed 48 h later. ARF rats had higher serum creatinine (1.3 +/- 0.2 mg/dl vs. 0.3 +/- 0.1), lower arterial pH (7.15 +/- 0.03 vs. 7.35 +/- 0.02), and higher fasting serum glucose (150 +/- 13 vs. 123 +/- 12 mg/dl) compared with control rats (P < 0.001 in all cases). The hypoglycemic effects of insulin and IGF-I were compared using euglycemic clamps. In control rats, rates of total body glucose uptake were not different during euglycemic insulin clamps at 2 mU.kg-1.min-1 and euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1. In rats with ARF, total body glucose uptake during euglycemic insulin clamps at 2 mU.kg-1.min-1 was significantly reduced (6.5 +/- 0.5 mg.kg-1.min-1) compared with controls (10.5 +/- 1.5 mg.kg-1.min-1, P < 0.01). In contrast, total body glucose uptake during euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1 in ARF rats (10.1 +/- 1.2 mg.kg-1.min-1) was not different from the corresponding value in control animals (10.3 +/- 1.3 mg.kg-1.min-1). Hepatic glucose production was suppressed by insulin equally but not suppressed by IGF-I in both groups. In a second experiment, ARF was induced by bilateral renal ischemia. The following groups of animals were studied: ARF + NaCl, ARF + NaHCO3, and control + NaCl. Insulin and IGF-I clamps were performed as above. Correction of acidosis partially corrected insulin resistance but did not affect IGF-I sensitivity. Thus the capacity of IGF-I infusion to stimulate glucose uptake is maintained in ARF rats, which are insulin resistant.