Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans

Aron Adkins, Rita Basu, Mai Persson, Betty Dicke, Pankaj Shah, Adrian Vella, W. Frederick Schwenk, Robert A. Rizza

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46 Scopus citations

Abstract

To determine the mechanism(s) by which insulin inhibits endogenous glucose production (EGP) in nondiabetic humans, insulin was infused at rates of 0.25, 0.375, or 0.5 mU · kg-1 · min-1 and glucose was clamped at ∼5.5 mmol/l. EGP, gluconeogenesis, and uridine-diphosphoglucose (UDP)-glucose flux were measured using [3- 3H]glucose, deuterated water, and the acetaminophen glucuronide methods, respectively. An increase in insulin from ∼75 to ∼100 to ∼150 pmol/l (∼12.5 to ∼17 to ∼25 μU/ml) resulted in progressive (ANOVA; P < 0.02) suppression of EGP (13.1 ± 1.3 vs. 11.7 ± 1.03 vs. 6.4 ± 2.15 μmol · kg-1 · min-1) that was entirely due to a progressive decrease (ANOVA; P < 0.05) in the contribution of glycogenolysis to EGP (4.7 ± 1.7 vs. 3.4 ± 1.2 vs. -2.1 ± 1.3 μmol · kg-1 · min-1). In contrast, both the contribution of gluconeogenesis to EGP (8.4 ± 1.0 vs. 8.3 ± 1.1 vs. 8.5 ± 1.3 μmol · kg-1 · min-1) and UDP-glucose flux (5.0 ± 0.4 vs. 5.0 ± 0.3 vs. 4.0 ± 0.5 μmol · kg-1 · min-1) remained unchanged. The contribution of the direct (extracellular) pathway to UDP-glucose flux was minimal and constant during all insulin infusions. We conclude that higher insulin concentrations are required to suppress the contribution of gluconeogenesis of EGP than are required to suppress the contribution of glycogenolysis to EGP in healthy nondiabetic humans. Since suppression of glycogenolysis occurred without a decrease in UDP-glucose flux, this implies that insulin inhibits EGP, at least in part, by directing glucose-6-phosphate into glycogen rather than through the glucose-6-phosphatase pathway.

Original languageEnglish (US)
Pages (from-to)2213-2220
Number of pages8
JournalDiabetes
Volume52
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Adkins, A., Basu, R., Persson, M., Dicke, B., Shah, P., Vella, A., Schwenk, W. F., & Rizza, R. A. (2003). Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans. Diabetes, 52(9), 2213-2220. https://doi.org/10.2337/diabetes.52.9.2213