Rizza R A, Haymond M W, Verdonk C A, Mandarino L J, Miles J M, Service F J, Gerich J E
Diabetes. 1981 May;30(5):377-81. doi: 10.2337/diab.30.5.377.
To determine the mechanism by which hyperinsulinemia causes hypoglycemia in insulinoma patients, rates of glucose production and utilization, and circulating levels of insulin, glucagon, alanine, lactate, and glycerol were measured in 6 insulinoma patients during development of fasting hypoglycemia and in 8 normal volunteers studied over an identical interval. Initially, insulinoma patients had a greater plasma insulin (42 +/- 9 versus 15 +/- 1 microunits/ml) and glucagon levels (214 +/- 31 versus 158 +/- 21 pg/ml) than normal subjects, P less than 0.05, but their plasma glucose levels (81 +/- 4 mg/dl) and rates of glucose production and utilization (1.71 +/- 0.08 and 1.74 +/- 0.08 mg/kg . min, respectively) were not significantly different from those of normal subjects (93 +/- 2 mg/dl, 1.93 +/- 0.11, and 1.92 +/- 0.13 mg/kg . min, respectively). During a subsequent 8-h fast, glucose production and glucose utilization decreased in both groups, but more markedly in insulinoma patients. Since glucose utilization exceeded glucose production to a greater extent in insulinoma patients than in normal subjects, plasma glucose decreased to 44 +/- 3 mg/dl in insulinoma patients, but only to 84 +/- 1 mg/dl in normal subjects (P less than 0.001). Glucose utilization in insulinoma patients never exceeded that of normal subjects. These results demonstrate that fasting hypoglycemia in the insulinoma patients is usually due to suppression of glucose production rather than to acceleration of glucose utilization, as is widely thought. A direct effect of insulin on the liver is probably responsible, since circulating levels of gluconeogenic precursors are normal and since plasma glucagon increases during development of hypoglycemia in insulinoma patients.
为了确定高胰岛素血症导致胰岛素瘤患者低血糖的机制，我们对6例胰岛素瘤患者在空腹低血糖发生过程中以及8名正常志愿者在相同时间段内的葡萄糖生成率、利用率以及胰岛素、胰高血糖素、丙氨酸、乳酸和甘油的循环水平进行了测量。最初，胰岛素瘤患者的血浆胰岛素水平（42±9对15±1微单位/毫升）和胰高血糖素水平（214±31对158±21皮克/毫升）高于正常受试者，P<0.05，但他们的血浆葡萄糖水平（81±4毫克/分升）以及葡萄糖生成率和利用率（分别为1.71±0.08和1.74±0.08毫克/千克·分钟）与正常受试者（分别为93±2毫克/分升、1.93±0.11和1.92±0.13毫克/千克·分钟）并无显著差异。在随后的8小时禁食期间，两组的葡萄糖生成和葡萄糖利用均下降，但胰岛素瘤患者下降更为明显。由于胰岛素瘤患者中葡萄糖利用超过葡萄糖生成的程度大于正常受试者，胰岛素瘤患者的血浆葡萄糖降至44±3毫克/分升，而正常受试者仅降至84±1毫克/分升（P<0.001）。胰岛素瘤患者的葡萄糖利用从未超过正常受试者。这些结果表明，胰岛素瘤患者的空腹低血糖通常是由于葡萄糖生成受到抑制，而非如广泛认为的那样是由于葡萄糖利用加速。胰岛素对肝脏的直接作用可能是原因所在，因为糖异生前体的循环水平正常，且在胰岛素瘤患者低血糖发生过程中血浆胰高血糖素会升高。
