IGF-I--stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM

• Published in: Diabetes (New York, N.Y.) Vol. 39; no. 9; pp. 1028 - 1032
• Main Authors: G L Dohm, C W Elton, M S Raju, N D Mooney, R DiMarchi, W J Pories, E G Flickinger, S M Atkinson, Jr, J F Caro
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-09-1990
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.39.9.1028

IGF-I--stimulated glucose transport in human skeletal muscle and IGF-I resistance in obesity and NIDDM.
G L Dohm ,
C W Elton ,
M S Raju ,
N D Mooney ,
R DiMarchi ,
W J Pories ,
E G Flickinger ,
S M Atkinson, Jr and
J F Caro
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858.
Abstract
Based on the observation that insulinlike growth factor I (IGF-I) can stimulate glucose utilization in nondiabetic subjects
and that the action of the IGF-I receptor is normal in the skeletal muscle of patients with non-insulin-dependent diabetes
mellitus (NIDDM), it seems possible that IGF-I might provide an effective acute treatment for the hyperglycemia of NIDDM.
Using our recently developed in vitro human muscle preparation, we investigated the hypothesis that IGF-I might be an effective
alternative to insulin in stimulating glucose transport in diabetic muscle. Abdominal muscle samples from nonobese nondiabetic,
obese nondiabetic, and obese NIDDM patients were obtained during elective abdominal surgery. Plasma levels of IGF-I in diabetic
patients were lower than those in either of the nondiabetic groups. Binding studies with wheat-germ-agglutinin-chromatography-purified
receptors demonstrated the presence of IGF-I receptors in human muscle, with IGF-I binding being approximately 24% that of
insulin. There was no change in IGF-I binding in muscle from obese or diabetic subjects, and the structural characteristics
of the IGF-I receptor were not altered, as determined by electrophoretic mobility. IGF-I stimulated glucose transport approximately
twofold in incubated muscle from control subjects, but there was no IGF-I stimulation of transport in muscle from obese subjects
with or without NIDDM. These results confirm a previous report that human muscle contains receptors for IGF-I and demonstrate
for the first time that IGF-I can stimulate glucose transport in human muscle. However, muscle from obese subjects with or
without NIDDM is resistant to the action of IGF-I.