Metabolic effects of hyperglycemia and hyperinsulinemia on fate of intracellular glucose in NIDDM.
Hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) stimulates peripheral glucose uptake, which tends to compensate for impaired insulin-mediated glucose uptake. The metabolic fate of glucose and suppression of fat oxidation may differ, however, when glucose uptake is stimulated primarily by insulin or hyperglycemia. To address this issue, three hyperinsulinemic glucose-clamp studies were performed in combination with indirect calorimetry in seven nonobese subjects with NIDDM. In the first two experiments, when glucose uptake was matched at approximately 8 mg.kg-1 fat-free mass (FFM).min-1 with primarily hyperinsulinemia (1350 +/- 445 pM) or hyperglycemia (20.8 +/- 1.8 mM), identical rates of glucose oxidation (3.21 +/- 0.29 and 3.10 +/- 0.23 mg.kg-1 FFM.min-1, NS) and nonoxidative glucose metabolism (5.19 +/- 0.75 and 5.46 +/- 0.61 mg.kg-1 FFM.min-1, NS) were achieved. When glucose uptake was increased further to 11.11 +/- 0.36 mg.kg-1 FFM.min-1 with less insulin (625 +/- 70 pM) and hyperglycemia, glucose oxidation (3.85 +/- 0.26 mg.kg-1 FFM.min-1) and nonoxidative glucose metabolism (7.26 +/- 0.51 mg.kg-1 FFM.min-1) rose significantly (both P less than 0.05 from matched studies at lower rates of glucose uptake). During all glucose-clamp studies, free fatty acids were comparably suppressed by 40-46% (all P less than 0.005 vs. basal values), whereas fat oxidation was suppressed by 70-80% (all P less than 0.005 vs. basal values). A strong negative correlation was observed between rates of glucose and fat oxidation (r = -0.88, P less than 0.001) when all studies were combined.(ABSTRACT TRUNCATED AT 250 WORDS)
Henry
R R
RR
Department of Medicine, Veterans Administration Medical Center, San Diego, CA 92161.
Gumbiner
B
B
Flynn
T
T
Thorburn
A W
AW
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002151:Calorimetry; D003920:Diabetes Mellitus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity; D010084:Oxidation-Reduction
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D005947:Glucose