Pancreatic α-cell dysfunction in diabetes
Pancreatic α-cell dysfunction in diabetes
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DOI：
10.1016/s1262-3636(08)73395-0
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发表时间：
2008-02-01
影响因子：
7.2
通讯作者：
Cani, P. D.
中科院分区：
文献类型：
--
作者：
Burcelin, R.;Knauf, C.;Cani, P. D.
2型糖尿病的一个主要特征是过量的肝脏葡萄糖生成和相应的胰岛素抵抗，导致空腹高血糖。为了提供解释这种损伤的生理和分子机制所做的大量工作导致了几个共识假设的出现。其中，2型糖尿病患者血浆胰高血糖素浓度每日升高且不调节。因此，旨在了解糖尿病期间胰高血糖素分泌的生理调节及其损害的研究与2型糖尿病的治疗直接相关。a细胞分泌胰高血糖素是对血糖降低的直接反应。胰高血糖素和其他反调节激素的异常分泌是1型和2型糖尿病的标志，也是使用强降糖药的主要限制。葡萄糖检测触发反调节的一些分子机制，特别是在高血糖发作时诱导胰高血糖素分泌或抑制胰高血糖素分泌，已经被确定。这些机制与胰岛素分泌β细胞的机制有关。葡萄糖转运体GLUT2和K-ATP依赖通道及其调控机制涉及中枢神经系统和肠脑激素GLP-1。在过去的几年里，糖甙在2型糖尿病患者血浆胰高血糖素浓度正常化方面提供了有希望的结果，这可以部分解释肠促胰岛素相关治疗的治疗效果。强调GLP-1调节胰高血糖素分泌的机制很可能与激素对门静脉和脑葡萄糖传感器的激活有关。当然，旨在恢复血糖调节的胰高血糖素分泌的策略是糖尿病患者治疗和预防医源性低血糖的重要里程碑。(C) 2008 Elsevier Masson SAS。版权所有。
A major, yet poorly understood, feature of type 2 diabetes is the excessive hepatic glucose production and the corresponding insulin resistance leading to fasting hyperglycaemia. The tremendous amount of work done to provide the physiological and molecular mechanisms explaining this impairment has led to the emergence of several consensual hypotheses. Among these, is the increased daily and unregulated plasma glucagon concentration in type 2 diabetic patients. Therefore, studies aiming to understand the physiological regulation of glucagon secretion and the corresponding impairment during diabetes are directly relevant to the treatment of type 2 diabetes. Glucagon secretion by a-cells is an immediate response to glucopenia. Abnormal secretion of glucagon and other counterregulatory hormones is a hallmark of type 1 and type 2 diabetes and a major limitation to the use of strong hypoglycaernia agents. A few Molecular mechanisms of glucose detection triggering counterregulation and in particular inducing glucagon secretion or suppressing it during hyperglycaemic episodes, have been identified. Such mechanisms are related to those of the insulin secreted beta-cell. The glucose transporter GLUT2 and the K-ATP dependent channel, as well as regulatory mechanisms, involved the central nervous system and the gut-brain hormone GLP-1. Over the last years, glucoineretins have provided promising results for the normalization of plasma glucagon concentration of type 2 diabetic patients, which could partly explain the therapeutic benefits of incretin-related therapy. The underlined mechanisrns of GLP-1 regulated glucagon secretion are most likely related to the action of the hormone on the activation of the portal and brain glucose sensors. Certainly, strategies aiming to restore glucose-regulated glucagon secretion are important milestones for the treatment of diabetic patient and the prevention of iatrogenic hypoglycaemia. (C) 2008 Elsevier Masson SAS. All rights reserved.