Ward W K, Beard J C, Halter J B, Porte D
Adv Exp Med Biol. 1985;189:137-58. doi: 10.1007/978-1-4757-1850-8_9.
In normal man, glucose serves to regulate basal insulin secretion by its participation with insulin in a feedback loop. In addition, glucose stimulates insulin secretion directly and potentiates insulin responses to nonglucose stimuli such as amino acids, beta-adrenergic stimuli, and gut hormones. Maximal glycemic potentiation of the acute insulin response to IV arginine occurs at a glucose level of approx. 450 mg/dl. In patients with noninsulin dependent diabetes mellitus (NIDDM), basal insulin levels have usually been reported as normal, but if plasma glucose is lowered to normal levels, a deficiency of basal insulin becomes apparent. In addition, the first phase (0-10 min) insulin response to IV glucose is absent in virtually all patients with overt NIDDM. In contrast, the second-phase (greater than 10 min) response is often preserved in NIDDM due to its maintenance by ambient hyperglycemia. Similarly, insulin responses to nonglucose stimuli such as arginine often appear normal in NIDDM because of potentiation by hyperglycemia. However, insulin responses to arginine are lower than those of nondiabetic controls when compared at multiple matched glucose levels. Indeed, maximal potentiation by glucose of the insulin response to arginine is markedly subnormal in NIDDM, suggesting a loss of functional B cell secretory capacity. In patients with long-standing insulin-dependent diabetes mellitus (IDDM), basal insulin secretion and insulin responses to all stimuli are virtually absent. However, in a remission phase, or in IDDM of short duration, basal insulin secretion and insulin responses to nonglucose stimuli may be relatively preserved. Therefore, islet dysfunction in IDDM and NIDDM, while etiologically different, share some common pathophysiological features.
在正常人中，葡萄糖通过与胰岛素参与反馈回路来调节基础胰岛素分泌。此外，葡萄糖直接刺激胰岛素分泌，并增强胰岛素对非葡萄糖刺激（如氨基酸、β-肾上腺素能刺激和肠道激素）的反应。静脉注射精氨酸后急性胰岛素反应的最大血糖增强作用发生在葡萄糖水平约为450mg/dl时。在非胰岛素依赖型糖尿病（NIDDM）患者中，基础胰岛素水平通常报告为正常，但如果将血浆葡萄糖降至正常水平，基础胰岛素缺乏就会变得明显。此外，几乎所有显性NIDDM患者对静脉注射葡萄糖的第一阶段（0-10分钟）胰岛素反应都不存在。相比之下，由于环境高血糖的维持，NIDDM患者的第二阶段（大于10分钟）反应通常得以保留。同样，由于高血糖的增强作用，NIDDM患者对精氨酸等非葡萄糖刺激的胰岛素反应通常看起来正常。然而，在多个匹配的葡萄糖水平下进行比较时，NIDDM患者对精氨酸的胰岛素反应低于非糖尿病对照组。事实上，NIDDM患者中葡萄糖对精氨酸胰岛素反应的最大增强作用明显低于正常水平，这表明功能性B细胞分泌能力丧失。在长期胰岛素依赖型糖尿病（IDDM）患者中，基础胰岛素分泌以及对所有刺激的胰岛素反应几乎都不存在。然而，在缓解期或病程较短的IDDM患者中，基础胰岛素分泌以及对非葡萄糖刺激的胰岛素反应可能相对保留。因此，IDDM和NIDDM中的胰岛功能障碍虽然病因不同，但具有一些共同的病理生理特征。
