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© 2001 by the American Diabetes Association, Inc.
Small Increases in Insulin Inhibit Hepatic Glucose Production Solely Caused by an Effect on Glycogen Metabolism
1 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee
2 Department of Medicine and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio
3 Diabetes Research and Training Center and Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York
Based on our earlier work, a 2.5-fold increase in insulin secretion should completely inhibit hepatic glucose production through the hormone’s direct effect on hepatic glycogen metabolism. The aim of the present study was to test the accuracy of this prediction and to confirm that gluconeogenic flux, as measured by three independent techniques, was unaffected by the increase in insulin. A 40-min basal period was followed by a 180-min experimental period in which an increase in insulin was induced, with euglycemia maintained by peripheral glucose infusion. Arterial and hepatic sinusoidal insulin levels increased from 10 ± 2 to 19 ± 3 and 20 ± 4 to 45 ± 5 µU/ml, respectively. Net hepatic glucose output decreased rapidly from 1.90 ± 0.13 to 0.23 ± 0.16 mg · kg-1 · min-1. Three methods of measuring gluconeogenesis and glycogenolysis were used: 1) the hepatic arteriovenous difference technique (n = 8), 2) the [14C]phosphoenolpyruvate technique (n = 4), and 3) the 2H2O technique (n = 4). The net hepatic glycogenolytic rate decreased from 1.72 ± 0.20 to -0.28 ± 0.15 mg · kg-1 · min-1 (P < 0.05), whereas none of the above methods showed a significant change in hepatic gluconeogenic flux (rate of conversion of phosphoenolpyruvate to glucose-6-phosphate). These results indicate that liver glycogenolysis is acutely sensitive to small changes in plasma insulin, whereas gluconeogenic flux is not.
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