Fasting hyperglycemia impairs glucose- but not insulin-mediated suppression of glucagon secretion
Fasting hyperglycemia impairs glucose- but not insulin-mediated suppression of glucagon secretion
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DOI：
10.1210/jc.2006-1515
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
DeFronzo, Ralph A.
中科院分区：
文献类型：
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作者：
Abdul-Ghani, Muhammad;DeFronzo, Ralph A.
目的：我们的目的是评估慢性高血糖对葡萄糖和胰岛素介导的α细胞分泌胰高血糖素的抑制作用。方法：对30例糖耐量正常、27例空腹糖耐量和/或糖耐量受损、32例2型糖尿病患者进行口服糖耐量试验（OGTT）和正糖高胰岛素钳夹。测定OGTT和胰岛素钳夹期间空腹血浆胰高血糖素浓度和血浆胰高血糖素浓度。结果：OGTT期间，血浆胰高血糖素浓度（曲线下面积）的下降与空腹血糖浓度呈负相关（r = -0.35; P < 0.001）。随着空腹血糖水平的升高，对血浆胰高血糖素的抑制作用逐渐减弱。相比之下，在正糖胰岛素钳夹期间，血浆胰高血糖素的抑制与空腹血糖浓度无关，并且在糖耐量正常、空腹糖耐量受损/糖耐量受损和糖尿病受试者中相似：分别为18%、23%和18%。结论：胰岛素介导的胰高血糖素分泌抑制与空腹血糖浓度无关，且不受慢性高血糖的影响。因此，OGTT期间血浆胰高血糖素抑制的缺陷很可能是由葡萄糖介导的胰高血糖素抑制受损引起的。空腹血浆葡萄糖浓度与胰高血糖素抑制降低之间的密切相关表明糖毒性作用对α细胞功能有影响。
Aim: Our aim was to assess the effect of chronic hyperglycemia on glucose- and insulin-mediated suppression of glucagon secretion by the alpha-cell.Methods: Thirty subjects with normal glucose tolerance, 27 with impaired fasting glucose and/or impaired glucose tolerance, and 32 type 2 diabetic subjects were studied with oral glucose tolerance test ( OGTT) and euglycemic hyperinsulinemic clamp. Fasting plasma glucagon concentration and plasma glucagon concentration during the OGTT and insulin clamp were measured.Results: During the OGTT, the decrement in the plasma glucagon concentration ( area under the curve) was correlated inversely with the fasting plasma glucose concentration ( r = -0.35; P < 0.001). As the fasting glucose level increased, the suppression of plasma glucagon progressively diminished. In contrast, during the euglycemic insulin clamp, the suppression of plasma glucagon was not correlated with the fasting plasma glucose concentration and was similar in subjects with normal glucose tolerance, subjects with impaired fasting glucose/impaired glucose tolerance, and diabetic subjects: 18, 23, and 18%, respectively.Conclusion: Insulin-mediated suppression of glucagon secretion is unrelated to the fasting plasma glucose concentration and is not impaired by chronic hyperglycemia. Thus, the defect in plasma glucagon suppression during the OGTT most likely results from impaired glucose-mediated glucagon suppression. The close correlation between fasting plasma glucose concentration and reduced glucagon suppression suggests a glucotoxic effect on alpha-cell function.