Insulin resistance limits glucose utilization and exercise
tolerance in a patient with myophosphorylase deficiency and
niddm.
Dorin, Richard I., James C. Field, Patrick J. Boyle, R. Philip Eaton,
Milton V. Icenogle.
Departments of Medicine and Biochemistry, Veterans Administration
Medical Center, University of New Mexico School of Medicine, and
Lovelace Research Foundation, Albuquerque, New Mexico
APStracts 3:0224A, 1996.
Myophosphorylase deficiency [McArdle's disease (MD)] produces a defect
in muscle glycogenolysis in which muscular work is limited by
delivery of external sources of substrate, primarily glucose and non
-esterified fatty acids (NEFA), to meet energy demands associated with
exercise. In the present study we evaluated an unusual patient with
both MD and non-insulin dependent diabetes mellitus (NIDDM). We
hypothesized that insulin resistance would limit transport of
extracellular glucose to skeletal muscle during exercise, resulting
in impaired exercise performance that was reversible by insulin
infusion. The effect of hyperinsulinemic "euglycemic" clamp
on exercise tolerance was evaluated by in vivo 31-phosphorous
magnetic resonance spectroscopy (31P-MRS) as well as total work
performed. We observed that insulin infusion significantly increased
the rate of systemic glucose utilization (P < 0.01) and also
significantly decreased the slope of Pi/PCr (P < 0.001) during
forearm exercise as compared to the control study. Insulin clamp was
also associated with an increase in total work performed (56%) during
exercise. Our findings demonstrate that resistance to the biological
actions of insulin, as occurs in type II diabetes mellitus, leads to
a defect in glucose transport that limits the availability of
extracellular glucose to exercising muscle. In our subject with a
substrate limited skeletal muscle metabolism (McArdle's disease),
reversal of this defect in insulin-dependent glucose transport by
hyperinsulinemic, euglycemic clamp was associated with significant
improvement in MRS parameters of skeletal muscle metabolism as well
as exercise performance.
Received 26 October 1995; accepted in final form 1 April 1996.
APS Manuscript Number A1144-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96