Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM

• Published in: Journal of applied physiology (1985) 1997-07, Vol.83 (1), p.166-171
• Main Authors: Simoneau, Jean-Aime, Kelley, David E
• Format: Article
• Language: English
• Subjects: Associated diseases and complications; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glycolysis - physiology; Humans; Insulin Resistance - physiology; Kinetics; Male; Medical sciences; Middle Aged; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Obesity - metabolism; Oxidation-Reduction
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1997.83.1.166

Jean-Aimé Simoneau 1 and David E. Kelley 2 , 3 1  Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Quebec, Canada G1V 4G2; 2  Department of Medicine, University of Pittsburgh, Pittsburgh 15261; and 3  Department of Veterans Affairs, Pittsburgh, Pennsylvania 15240 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. 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