Lewis G F, Steiner G, Polonsky K S, Weller B, Zinman B
Department of Medicine, University of Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 1994 Jul;79(1):66-70. doi: 10.1210/jcem.79.1.8027255.
We describe a new noninvasive method for comparing insulin secreted acutely by the pancreas vs. a matched peripheral venous insulin infusion in humans. An intravenous tolbutamide infusion algorithm was developed that produced sustained steady rates of portal insulin secretion over 5 h in 11 healthy young men. Plasma glucose levels were maintained in the euglycemic range by adjusting the rate of an iv dextrose (20%) infusion. The pancreatic insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution using standard parameters for a two-compartment mathematical model for C-peptide distribution and metabolism. On a subsequent occasion in the same subject, exogenous insulin was infused peripherally at a rate that matched the earlier tolbutamide-induced pancreatic insulin secretory rate, and euglycemia was maintained with a variable 20% dextrose infusion. The assumption that tolbutamide, when used in this fashion, has no independent insulin-like or insulin-potentiating effect at either low or high levels of peripheral insulinemia, does not affect insulin clearance, and does not suppress peripheral glucagon levels was validated in four patients with insulin-dependent diabetes mellitus. Mean peripheral immunoreactive insulin was significantly higher in the insulin infusion study than in the tolbutamide study (286 +/- 31 vs. 156 +/- 21 pmol/L; P = 0.0001). The dextrose infusion rates required to maintain euglycemia were also higher in the insulin infusion study (0.44 +/- 0.03 vs. 0.32 +/- 0.03 mmol/kg.min; P = 0.003). The MCR of insulin was greater in the tolbutamide infusion vs. the exogenous insulin infusion study (32.6 +/- 2.9 vs. 19.8 +/- 2.2 mL/kg.min; P = 0.0003), probably due to the hepatic first pass effect on insulin clearance when insulin is delivered by the portal route. This noninvasive method can be used in future studies to examine the relative importance of direct hepatic vs. peripheral effects of insulin in controlling hepatic glucose and lipid production.
我们描述了一种新的非侵入性方法，用于比较人类胰腺急性分泌的胰岛素与外周静脉输注匹配胰岛素的情况。开发了一种静脉注射甲苯磺丁脲的输注算法，该算法在11名健康年轻男性中产生了5小时持续稳定的门静脉胰岛素分泌率。通过调整静脉注射葡萄糖（20%）的输注速率，将血浆葡萄糖水平维持在正常血糖范围内。使用C肽分布和代谢的两室数学模型的标准参数，通过反卷积从外周C肽水平计算胰腺胰岛素分泌率。在同一受试者的后续实验中，以与早期甲苯磺丁脲诱导的胰腺胰岛素分泌率相匹配的速率外周输注外源性胰岛素，并通过可变的20%葡萄糖输注维持正常血糖。在4例胰岛素依赖型糖尿病患者中验证了以下假设：以这种方式使用时，甲苯磺丁脲在低或高外周胰岛素血症水平下没有独立的胰岛素样或胰岛素增强作用，不影响胰岛素清除率，也不抑制外周胰高血糖素水平。胰岛素输注研究中的平均外周免疫反应性胰岛素显著高于甲苯磺丁脲研究（286±31对156±21 pmol/L；P = 0.0001）。胰岛素输注研究中维持正常血糖所需的葡萄糖输注速率也更高（0.44±0.03对0.32±0.03 mmol/kg·min；P = 0.003）。与外源性胰岛素输注研究相比，甲苯磺丁脲输注时胰岛素的代谢清除率更高（32.6±2.9对19.8±2.2 mL/kg·min；P = 0.0003），这可能是由于门静脉途径输送胰岛素时肝脏对胰岛素清除的首过效应。这种非侵入性方法可用于未来的研究，以检验胰岛素直接肝脏效应与外周效应在控制肝脏葡萄糖和脂质生成中的相对重要性。
