Glucose metabolism in incubated human muscle: effect of obesity and non-insulin-dependent diabetes mellitus.
Skeletal muscle contributes significantly to reduced insulin-stimulated glucose disposal in patients with obesity and non-insulin-dependent (type II) diabetes mellitus (NIDDM). The biochemical basis for insulin resistance is not known but may involve reduced glucose transport and/or a defect in intracellular pathways for glucose disposal. To address this question, we measured basal and insulin-stimulated glucose oxidation, glycogen formation, and nonoxidative glycolysis (lactate and amino acid release) in an incubated muscle preparation from nonobese and morbidly obese patients with and without NIDDM. Pathways of glucose disposal were also determined in muscle of obese NIDDM patients incubated under hyperglycemic (20 mmol/L) conditions, which increases glucose uptake by mass action. Under basal conditions (no insulin present) there were no significant differences in glycogen formation or glucose oxidation between nonobese control, obese nondiabetic, or obese diabetics. Lactate release was significantly higher in obese controls compared to nonobese controls in the basal state at 5 mmol/L glucose (10.2 +/- 2.8 v 24.7 +/- 3.5 nmol/min/g, P < .05). Under maximal insulin-stimulated conditions, rates of glycogen formation, glucose oxidation, and nonoxidized glycolysis increased 1.9-, 2.3-, and 2.2-fold over basal (P < .05) in nonobese controls. By contrast, insulin was ineffective at stimulating significant increases in any metabolic pathway of glucose disposal in muscle of obese or obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Friedman
J E
JE
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858.
Caro
J F
JF
Pories
W J
WJ
Azevedo
J L
JL
Dohm
G L
GL
D000328:Adult; D000704:Analysis of Variance; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D009765:Obesity; D009767:Obesity, Morbid / Q000378:metabolism*; D010084:Oxidation-Reduction
D007328:Insulin; D006003:Glycogen; D005947:Glucose