Insulin-like growth factor-i action on glucose transport in acute
renal failure.
Mak, Robert H. K., and Otto Mehls.
DEPARTMENT OF PEDIATRICS, STANFORD UNIVERSITY SCHOOL OF MEDICINE,
STANFORD, CA., U.S.A.;, DIVISION OF PEDIATRIC NEPHROLOGY, UNIVERSITY
CHILDREN'S HOSPITAL, HEIDELBERG, FEDERAL REPUBLIC OF GERMANY
APStracts 3:0079F, 1996.
Insulin resistance is common in acute renal failure (ARF). Insulin
-like growth factor (IGF)-I has insulin-like actions. The present
study is 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 hours 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 mg/dl Vs 123 + 12) compared
with control rats (p &LT 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 [mu]g.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/min)
compared with controls (10.5 + 1.5 mg.kg-1.min-1; p&LT0.01). In
contrast, total body glucose uptake during euglycemic IGF-I clamps at
5 [mu]g.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.
Received 10 November 1996; accepted in final form 29 March 1996.
APS Manuscript Number F381-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96