Ward W K, Bolgiano D C, McKnight B, Halter J B, Porte D
J Clin Invest. 1984 Oct;74(4):1318-28. doi: 10.1172/JCI111542.
In order to assess whether patients with noninsulin-dependent diabetes mellitus (NIDDM) possess normal insulin secretory capacity, maximal B cell responsiveness to the potentiating effects of glucose was estimated in eight untreated patients with NIDDM and in eight nondiabetic controls. The acute insulin response to 5 g intravenous arginine was measured at five matched plasma glucose levels that ranged from approximately 100-615 mg/dl. The upper asymptote approached by acute insulin responses (AIRmax) and the plasma glucose concentration at half-maximal responsiveness (PG50) were estimated using nonlinear regression to fit a modification of the Michaelis-Menten equation. In addition, glucagon responses to arginine were measured at these same glucose levels to compare maximal A cell suppression by hyperglycemia in diabetics and controls. Insulin responses to arginine were lower in diabetics than in controls at all matched glucose levels (P less than 0.001 at all levels). In addition, estimated AIRmax was much lower in diabetics than in controls (83 +/- 21 vs. 450 +/- 93 microU/ml, P less than 0.01). In contrast, PG50 was similar in diabetics and controls (234 +/- 28 vs. 197 +/- 20 mg/dl, P equals NS) and insulin responses in both groups approached or attained maxima at a glucose level of approximately 460 mg/dl. Acute glucagon responses to arginine in patients with NIDDM were significantly higher than responses in controls at all glucose levels. In addition, although glucagon responses in control subjects reached a minimum at a glucose level of approximately 460 mg/dl, responses in diabetics declined continuously throughout the glucose range and did not reach a minimum. Thus, A cell sensitivity to changes in glucose level may be diminished in patients with NIDDM. In summary, patients with NIDDM possess markedly decreased maximal insulin responsiveness to the potentiating effects of glucose. Such a defect indicates the presence of a reduced B cell secretory capacity and suggests a marked generalized impairment of B cell function in patients with NIDDM.
为了评估非胰岛素依赖型糖尿病（NIDDM）患者是否具有正常的胰岛素分泌能力，我们对8例未经治疗的NIDDM患者和8例非糖尿病对照者的胰岛B细胞对葡萄糖增强作用的最大反应性进行了评估。在5个匹配的血浆葡萄糖水平（范围约为100 - 615mg/dl）下，测量了静脉注射5g精氨酸后的急性胰岛素反应。使用非线性回归拟合米氏方程的修正形式，估算急性胰岛素反应的上限（AIRmax）和半最大反应性时的血浆葡萄糖浓度（PG50）。此外，在相同的葡萄糖水平下测量了精氨酸刺激后的胰高血糖素反应，以比较糖尿病患者和对照者中高血糖对胰岛A细胞的最大抑制作用。在所有匹配的葡萄糖水平下，糖尿病患者对精氨酸的胰岛素反应均低于对照者（所有水平P均小于0.001）。此外，估算的糖尿病患者AIRmax远低于对照者（83±21对450±93μU/ml，P小于0.01）。相比之下，糖尿病患者和对照者的PG50相似（234±28对197±20mg/dl，P等于无显著性差异），两组的胰岛素反应在葡萄糖水平约为460mg/dl时接近或达到最大值。NIDDM患者对精氨酸的急性胰高血糖素反应在所有葡萄糖水平下均显著高于对照者。此外，尽管对照者的胰高血糖素反应在葡萄糖水平约为460mg/dl时达到最小值，但糖尿病患者的反应在整个葡萄糖范围内持续下降，未达到最小值。因此，NIDDM患者的胰岛A细胞对葡萄糖水平变化的敏感性可能降低。总之，NIDDM患者对葡萄糖增强作用的最大胰岛素反应性显著降低。这种缺陷表明胰岛B细胞分泌能力下降，并提示NIDDM患者存在明显的广泛性B细胞功能损害。
