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1 Physical Activity Sciences
Laboratory, Laval University, Ste-Foy, Quebec, Canada G1V 4G2;
2 Department of Medicine,
Received 20 August 1996; accepted in final form 3 March 1997.
Simoneau, Jean-Aimé, and David E. Kelley. Altered
glycolytic and oxidative capacities of skeletal muscle contribute to
insulin resistance in NIDDM. J. Appl.
Physiol. 83(1): 166-171, 1997.
obesity; non-insulin-dependent diabetes mellitus; muscle enzymes; hexokinase; citrate synthase; phosphofructokinase
The insulin
resistance of skeletal muscle in glucose-tolerant obese individuals is
associated with reduced activity of oxidative enzymes and a
disproportionate increase in activity of glycolytic enzymes. Because
non-insulin-dependent diabetes mellitus (NIDDM) is a disorder
characterized by even more severe insulin resistance of skeletal muscle
and because many individuals with NIDDM are obese, the present study
was undertaken to examine whether decreased oxidative and increased
glycolytic enzyme activities are also present in NIDDM. Percutaneous
biopsy of vatus lateralis muscle was obtained in eight lean (L) and
eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects
and was assayed for marker enzymes of the glycolytic
[phosphofructokinase, glyceraldehyde phosphate dehydrogenase,
hexokinase (HK)] and oxidative pathways [citrate synthase
(CS), cytochrome-c oxidase], as
well as for a glycogenolytic enzyme (glycogen phosphorylase) and a
marker of anaerobic ATP resynthesis (creatine kinase). Insulin
sensitivity was measured by using the euglycemic clamp technique.
Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye
phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum
velocity for oxidative enzymes (CS,
cytochrome-c oxidase) was lowest in subjects with NIDDM. The ratio between glycolytic and
oxidative enzyme activities within skeletal muscle correlated
negatively with insulin sensitivity. The HK/CS ratio had the strongest
correlation (r = 
0.60, P < 0.01) with insulin
sensitivity. In summary, an imbalance between glycolytic and oxidative
enzyme capacities is present in NIDDM subjects and is more severe than
in obese or lean glucose-tolerant subjects. The altered ratio between
glycolytic and oxidative enzyme activities found in skeletal muscle of
individuals with NIDDM suggests that a dysregulation between
mitochondrial oxidative capacity and capacity for glycolysis is an
important component of the expression of insulin resistance.
0161-7567/97 $5.00
Copyright © 1997 the American Physiological Society
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