Insulin resistance limits glucose utilization and exercise tolerance in myophosphorylase deficiency and NIDDM.
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 nonesterified fatty acids, 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. 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 a hyperinsulinemic "euglycemic" clamp on exercise tolerance was evaluated by in vivo 31P-magnetic resonance spectroscopy 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 ratio of inorganic phosphate to phosphocreatine (P < 0.001) during forearm exercise compared with 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 (MD), reversal of this defect in insulin-dependent glucose transport by a hyperinsulinemic euglycemic clamp was associated with significant improvement in magnetic resonance spectroscopy parameters of skeletal muscle metabolism as well as exercise performance.
Dorin
R I
RI
Department of Medicine, Veterans Affairs Medical Center, University of New Mexico School of Medicine, Albuquerque, USA.
Field
J C
JC
Boyle
P J
PJ
Eaton
R P
RP
Icenogle
M V
MV
D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D017079:Exercise Tolerance / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006012:Glycogen Storage Disease Type V / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D006005:Phosphorylases / Q000378:metabolism*
D006005:Phosphorylases; D005947:Glucose