Division of Endocrinology, Metabolism, and Lipid Research, Washington University, St. Louis, Missouri 63110, USA.
Endocrinology. 2012 Mar;153(3):1039-48. doi: 10.1210/en.2011-1499. Epub 2011 Dec 13.
Pancreatic islet α-cell glucagon secretion is critically dependent on pancreatic islet β-cell insulin secretion. Normally, a decrease in the plasma glucose concentration causes a decrease in β-cell insulin secretion that signals an increase in α-cell glucagon secretion during hypoglycemia. In contrast, an increase in the plasma glucose concentration, among other stimuli, causes an increase in β-cell insulin secretion that signals a decrease, or at least no change, in α-cell glucagon secretion after a meal. In absolute endogenous insulin deficiency (i.e. in type 1 diabetes and in advanced type 2 diabetes), however, β-cell failure results in no decrease in β-cell insulin secretion and thus no increase in α-cell glucagon secretion during hypoglycemia and no increase in β-cell insulin secretion and thus an increase in α-cell glucagon secretion after a meal. In type 1 diabetes and advanced type 2 diabetes, the absence of an increment in glucagon secretion, in the setting of an absent decrement in insulin secretion and an attenuated increment in sympathoadrenal activity, in response to falling plasma glucose concentrations plays a key role in the pathogenesis of iatrogenic hypoglycemia. In addition, there is increasing evidence that, in the aggregate, suggests that relative hyperglucagonemia, in the setting of deficient insulin secretion, plays a role in the pathogenesis of hyperglycemia in diabetes. If so, abnormal glucagon secretion is involved in the pathogenesis of both hypoglycemia and hyperglycemia in diabetes.
胰岛 α 细胞胰高血糖素的分泌对胰岛 β 细胞胰岛素的分泌有严格的依赖性。通常，血糖浓度降低会导致 β 细胞胰岛素分泌减少，从而在低血糖时信号增加 α 细胞胰高血糖素分泌。相比之下，血糖浓度升高（以及其他刺激因素）会导致 β 细胞胰岛素分泌增加，从而在餐后信号减少或至少不变 α 细胞胰高血糖素分泌。然而，在绝对内源性胰岛素缺乏（即 1 型糖尿病和晚期 2 型糖尿病）中，β 细胞衰竭导致β细胞胰岛素分泌没有减少，因此在低血糖期间没有增加 α 细胞胰高血糖素分泌，也没有增加β细胞胰岛素分泌，因此在餐后增加 α 细胞胰高血糖素分泌。在 1 型糖尿病和晚期 2 型糖尿病中，在胰岛素分泌没有减少、交感肾上腺活性增加而胰高血糖素分泌没有增加的情况下，血糖浓度下降时缺乏胰高血糖素分泌的增加，在医源性低血糖的发病机制中起着关键作用。此外，越来越多的证据表明，在胰岛素分泌不足的情况下，相对高血糖素血症总体上可能在糖尿病高血糖的发病机制中起作用。如果是这样，异常的胰高血糖素分泌可能参与了糖尿病低血糖和高血糖的发病机制。
