GLUT4 Is Reduced in Slow Muscle Fibers of Type 2 Diabetic Patients
Is Insulin Resistance in Type 2 Diabetes a Slow, Type 1 Fiber Disease?
- 1Pathology and
- 2Endocrinology, Odense University Hospital, Odense, Denmark
- 3Department of Clinical Biochemistry, Aarhus University Hospital, Denmark
To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic patients was reduced by 9% compared with the weight-matched obese subjects and by 18% compared with the lean control group. The slow-fiber fraction was reduced to 86% in the obese subjects and to 75% in the diabetic subjects compared with the control group. Estimated GLUT4 contribution from slow fibers was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes and thus contribute to skeletal muscle insulin resistance.
Address correspondence and reprint requests to Michael Gaster, Department of Pathology, Odense University Hospital, DK-5000 Odense, DK-Denmark. E-mail (secretary):.
Received for publication 24 August 2000 and accepted in revised form 21 February 2001.
f-GLUT4, GLUT4 contribution from fast-twitch fibers; HRP, horseradish peroxidase; s-GLUT4, GLUT4 contribution from slow-twitch fibers.