Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (∼7 and 10 mg · kg−1 fat-free mass [FFM] · min−1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg · kg−1 FFM · min−1), there was less suppression of both FFA (33 vs. 43%, P < 0.05) and Fox (73 vs. 90%, P < 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg · kg−1 FFM · min−1 P < 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg · kg−1 FFM · min−1) required >300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both >90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg · kg−1 FFM · min−1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism.
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Original Articles|
January 01 1990
Effect of Hyperinsulinemia and Hyperglycemia on Intracellular Glucose and Fat Metabolism in Healthy Subjects
Anne W Thorburn;
Anne W Thorburn
Department of Medicine, University of California, and the Metabolism Division, Veterans Administration Medical Center
San Diego, California
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Barry Gumbiner;
Barry Gumbiner
Department of Medicine, University of California, and the Metabolism Division, Veterans Administration Medical Center
San Diego, California
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Ginger Brechtel;
Ginger Brechtel
Department of Medicine, University of California, and the Metabolism Division, Veterans Administration Medical Center
San Diego, California
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Robert R Henry
Robert R Henry
Department of Medicine, University of California, and the Metabolism Division, Veterans Administration Medical Center
San Diego, California
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Address correspondence and reprint requests to Robert R. Henry, MD, Veterans Administration Medical Center (V-111G), 3350 La Jolla Village Drive, San Diego, CA 92161.
Diabetes 1990;39(1):22–30
Article history
Received:
May 08 1989
Revision Received:
August 28 1989
Accepted:
August 28 1989
PubMed:
2210057
Citation
Anne W Thorburn, Barry Gumbiner, Ginger Brechtel, Robert R Henry; Effect of Hyperinsulinemia and Hyperglycemia on Intracellular Glucose and Fat Metabolism in Healthy Subjects. Diabetes 1 January 1990; 39 (1): 22–30. https://doi.org/10.2337/diacare.39.1.22
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