Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans
Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans
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DOI：
10.2337/diabetes.52.9.2213
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发表时间：
2003-09-01
期刊：
影响因子：
7.7
通讯作者：
Rizza, R
中科院分区：
文献类型：
--
作者：
Adkins, A;Basu, R;Rizza, R
为了确定胰岛素抑制非糖尿病患者内源性葡萄糖生成（EGP）的机制，以0.25、0.375或0.5 mU的速率输注胰岛素。kg（-1）。min（-1），葡萄糖钳夹至5.5mmol/l。EGP、尿苷生成和尿苷-二磷酸葡萄糖（UDP）-葡萄糖通量分别使用[3-H-3]葡萄糖、氘代水和对乙酰氨基酚葡萄糖醛酸苷方法测量。胰岛素水平从接近75 pmol/l增加到接近100 pmol/l，再增加到接近150 pmol/l（接近12.5 μ U/ml，接近17 μ U/ml，接近25 μ U/ml），导致EGP的进行性（方差分析; P < 0.02）抑制（13.1 +/- 1.3 vs. 11.7 +/- 1.03 vs. 6.4 +/- 2.15 mumol . kg（-1）。min（-1）），这完全是由于糖原分解对EGP的贡献（4.7 +/- 1.7 vs. 3.4 +/- 1.2 vs. -2.1 +/- 1.3 mumol . kg（-1）。min（-1））。相比之下，糖异生对EGP的贡献（8.4 +/- 1.0 vs. 8.3 +/- 1.1 vs. 8.5 +/- 1.3 mumol .）kg（-1）。min（-1））和UDP-葡萄糖通量（5.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.0 +/- 0.5 mumol . kg（-1）。min（-1））保持不变。在所有胰岛素输注期间，直接（细胞外）途径对UDP-葡萄糖通量的贡献极小且恒定。我们的结论是，需要更高的胰岛素浓度，以抑制EGP的糖原分解的贡献比所需的健康非糖尿病人类抑制EGP的糖原分解的贡献。由于糖原分解的抑制发生在UDP-葡萄糖通量没有减少的情况下，这意味着胰岛素抑制EGP，至少部分是通过将葡萄糖-6-磷酸导入糖原而不是通过葡萄糖-6-磷酸酶途径。
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 similar to5.5 mmol/l. EGP, gluconeogenesis, and uridine-diphosphoglucose (UDP)-glucose flux were measured using [3-H-3]glucose, deuterated water, and the acetaminophen glucuronide methods, respectively. An increase in insulin from similar to75 to similar to100 to similar to150 pmol/l (similar to12.5 to similar to17 to similar to25 muU/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 mumol . 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 mumol . 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 mumol . kg(-1) . min(-1)) and UDP-glucose flux (5.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.0 +/- 0.5 mumol . 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.