Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion.
Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion.
复制标题
人类餐后血糖反调节机制。
DOI：
10.1172/jci110967
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Cryer,PE
中科院分区：
文献类型：
--
作者：
Tse,TF;Clutter,WE;Shah,SD;Cryer,PE
葡萄糖摄入后从外源性葡萄糖输送到内源性葡萄糖产生的转变不仅仅归因于胰岛素的耗散，因此还必须涉及主动升高血浆葡萄糖浓度的因素——葡萄糖反调节因素。我们已经证明，其中两种胰高血糖素和肾上腺素的分泌对于葡萄糖摄入具有特异性，并且在时间上与葡萄糖反调节过程相关。为了确定胰高血糖素和肾上腺素在餐后血糖反调节中的生理作用，我们制定了药物干预措施，在正常受试者摄入 75 g 葡萄糖后 225 分钟开始，导致内源性胰高血糖素缺乏（有或没有外源性胰高血糖素替代）、肾上腺素能阻滞以及肾上腺素能阻滞加上胰高血糖素缺乏。此外，我们还评估了双侧肾上腺切除受试者中单独的内源性肾上腺素缺乏以及葡萄糖摄入后后期与胰高血糖素缺乏相结合的影响。胰高血糖素缺乏导致最低血浆葡萄糖浓度比对照值低约 30%（P 小于 0.01），但在摄入葡萄糖后不会导致低血糖。这种效应可以通过胰高血糖素替代来预防。单独的肾上腺素能阻断和肾上腺素缺乏都不会损害葡萄糖反调节过程。然而，胰高血糖素和肾上腺素的联合缺乏导致平均血浆葡萄糖在摄入葡萄糖后逐渐下降至低血糖水平；这些患者的最终葡萄糖浓度比对照（肾上腺素缺乏）值低 40%（P 小于 0.02），比正常受试者的对照值低近 50%（P 小于 0.001），比胰高血糖素缺乏值低约 30%（P 小于 0.05）。我们得出结论：（a）葡萄糖摄入后期从外源性葡萄糖输送到内源性葡萄糖产生的转变是胰岛素分泌协调减少和胰高血糖素分泌恢复的结果。 (b) 肾上腺素通常在此过程中不起关键作用，但当胰高血糖素分泌不足时，肾上腺素分泌增强可在很大程度上补偿并防止低血糖。图片图1图2图3图4图5图6图7图8图9
The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.ImagesFIGURE 1FIGURE 2FIGURE 3FIGURE 4FIGURE 5FIGURE 6FIGURE 7FIGURE 8FIGURE 9