Hepatic glucose production is regulated both by direct hepatic and extrahepatic effects of insulin in humans
Hepatic glucose production is regulated both by direct hepatic and extrahepatic effects of insulin in humans
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DOI：
10.2337/diabetes.45.4.454
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发表时间：
1996-04-01
期刊：
影响因子：
7.7
通讯作者：
Giacca, A
中科院分区：
文献类型：
--
作者：
Lewis, GF;Zinman, B;Giacca, A
本研究考察了胰岛素给药途径对人体葡萄糖周转的影响。用一种新的无创性体内方法，可以比较胰腺分泌胰岛素的急性效应和外周静脉注射胰岛素的急性效应。在三项正常血糖-高胰岛素研究中，第一项研究(n=10)采用程序化静脉滴注甲苯丁胺的方法造成恒定性门脉高胰岛素血症，胰岛素分泌率由外周血浆C-肽水平反卷积得到。在第二组(n=10)中，外源性胰岛素的外周静脉输注率与第一组相同，在第三组(n=7)中，第一组的外周胰岛素水平与第一组相同，外源性胰岛素的输注率减半，外周胰岛素水平较高(P<；门脉胰岛素输注(266.3+/-30.4pmol/L)和门静脉胰岛素输注(171.1+/-30.4pmol/L)或半速胰岛素输注(158.6+/-7.4pmol/L)(门静脉与半速外周胰岛素输注，NS)相比，前者(0.001)明显低于后者。门脉胰岛素研究计算的肝脏胰岛素水平(443.1+/-52.6pmol/L)高于充盈率外周胰岛素研究(303.6+/-30.9pmol/L)或半速外周胰岛素研究(204.5+/-9.8pmol/L)(P<；0.001)，全速外周胰岛素输注对肝脏葡萄糖生成的抑制程度更大(69.3+/-7.8%，P<；；门静脉或半速外周胰岛素输注(0.001.3%±9.8%)明显高于门脉或半速外周胰岛素输注(36.8+/-3.8%)。然而，在门脉胰岛素研究中，尽管外周胰岛素水平相同，但抑制程度大于外周胰岛素半衰期研究(P<；0.01)。在5名C肽阴性的IDDM患者中，甲苯丁胺以这种方式使用时，对葡萄糖周转、胰高血糖素或糖异生前体和糖异生的能量底物没有独立影响的假设得到了验证。我们的结论是，在非糖尿病人中，1)胰岛素的外周效应在抑制HGP方面很重要，这一点从外周与门静脉胰岛素输送等效率对HGP的抑制更大程度上得到了证明；2)由于门静脉胰岛素与外周胰岛素水平匹配时HGP受到更大程度的抑制，当外周胰岛素水平匹配时，胰岛素诱导的HGP抑制也部分地由直接的肝脏效应介导。
The present study examines the effect of the route of insulin delivery on glucose turnover in humans. By using a new noninvasive in vivo method, the acute effect of insulin secreted by we pancreas can be compared with that of insulin delivered by a peripheral vein, Three euglycemic-hyperinsulinemic studies were performed in lean healthy men, in the first study (n = 10), constant portal hyperinsulinemia was produced using a programmed intravenous tolbutamide infusion algorithm, and the insulin secretion rate was mathematically derived by deconvolution from peripheral plasma C-peptide levels. In the second study (n = 10), exogenous insulin was infused by peripheral vein at the same rate as that determined in the first study, in the third study (n = 7), the peripheral insulin levels in the first study were matched by infusing exogenous insulin into a peripheral vein at half that rate, Peripheral insulin levels were higher (P < 0.001) with the full-rate peripheral insulin infusion (266.3 +/- 28.1 pmol/l) than with the portal delivery of insulin (171.1 +/- 30.4 pmol/l) or the half-rate peripheral insulin infusion (158.6 +/- 7.4 pmol/l) (portal versus half-rate peripheral insulin infusion, NS). Calculated hepatic insulin levels were higher (P < 0.001) in the portal insulin study (443.1 +/- 52.6 pmol/l) than in tile fill-rate peripheral insulin study (303.6 +/- 30.9 pmol/l) or in the half-rate peripheral insulin study (204.5 +/- 9.8 pmol/l), Hepatic glucose production (HGP) was suppressed to a greater extent with the full-rate peripheral insulin infusion (69.3 +/- 7.8%, P < 0.001 vs, portal or half-rate peripheral insulin) than portal (50.3 +/- 9.8%) or half-rate peripheral insulin infusion (36.8 +/- 3.8%). In the portal insulin study, however, suppression was greater than in the half-rate peripheral insulin study (P < 0.01), in spite of equal peripheral insulin levels. The assumption that tolbutamide, when used in this fashion, has no independent effect on glucose turnover, glucagon, or gluconeogenic precursor and energy substrates for gluconeogenesis was validated in five C-peptide-negative patients with IDDM. We conclude that in nondiabetic humans, 1) peripheral effects of insulin are important in suppressing HGP, as evidenced by the greater suppression of HGP with equivalent rate peripheral versus portal insulin delivery, and 2) because HGP was suppressed to a greater extent with portal versus peripheral insulin delivery at half the rate when peripheral insulin levels were matched, insulin-induced suppression of HGP is also partly mediated by a direct hepatic effect.