TY - JOUR
T1 - Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans
AU - Adkins, Aron
AU - Basu, Rita
AU - Persson, Mai
AU - Dicke, Betty
AU - Shah, Pankaj
AU - Vella, Adrian
AU - Schwenk, W. Frederick
AU - Rizza, Robert A.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
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U2 - 10.2337/diabetes.52.9.2213
DO - 10.2337/diabetes.52.9.2213
M3 - Article
C2 - 12941759
AN - SCOPUS:0042320958
SN - 0012-1797
VL - 52
SP - 2213
EP - 2220
JO - Diabetes
JF - Diabetes
IS - 9
ER -