Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM. Evidence for primary defect in glucose transport and/or phosphorylation but not oxidation.
Insulin-stimulated glucose oxidation is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this decrease is due to a primary defect in the oxidative pathway or is secondary to impaired glucose transport and/or phosphorylation. To address this issue, glucose oxidation was measured under steady-state conditions at low (approximately 270 pmol) and high (approximately 17 mumol) insulin concentrations in seven patients with NIDDM and seven healthy nondiabetic subjects matched for sex, age, and obesity. Glucose oxidation was measured simultaneously by indirect calorimetry and the isotopedilution technique. Although glucose oxidation and nonoxidative storage were lower (P less than 0.05) in diabetic than nondiabetic subjects during the low- and high-dose insulin infusions, oxidation of intracellularly derived glucose, estimated by subtracting the rate of oxidation measured isotopically (i.e., glucose oxidation derived from the extracellular space) from that measured by indirect calorimetry (i.e., total glucose oxidation), did not differ in diabetic and nondiabetic subjects during the low-dose insulin infusion (3.3 +/- 0.1 vs. 3.0 +/- 0.1 mumol.kg-1.min-1). Both techniques provided identical estimates of glucose oxidation during the high-dose insulin infusion. Impaired oxidation of extracellularly but not intracellularly derived glucose strongly suggests that the cause of decreased glucose oxidation in patients with NIDDM is secondary to impaired glucose transport and/or phosphorylation rather than a primary abnormality in the oxidative pathway.
Butler
P C
PC
Department of Medicine, Mayo Clinic, Rochester, MN 55905.
Kryshak
E J
EJ
Marsh
M
M
Rizza
R A
RA
D000328:Adult; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D002151:Calorimetry; D002245:Carbon Dioxide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation
D001639:Bicarbonates; D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D002245:Carbon Dioxide; D005947:Glucose; D010100:Oxygen