Insulin-like growth factor-I action on glucose transport in acute renal failure.
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.
Mak
R H
RH
Department of Pediatrics, Stanford University School of Medicine, California 94305-5119, USA.
Mehls
O
O
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I