Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cells.
Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cells.
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DOI：
10.1016/j.pbiomolbio.2011.07.005
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Holz GG
中科院分区：
文献类型：
--
作者：
Leech CA;Dzhura I;Chepurny OG;Kang G;Schwede F;Genieser HG;Holz GG
胰高血糖素样肽-1（GLP-1）刺激胰腺β细胞分泌胰岛素，GLP-1是一种降糖激素，在进食后从远端肠的肠内分泌L细胞释放。GLP-1模拟物（例如，Byetta）和GLP-1类似物（例如，诺和力）激活β细胞GLP-1受体（GLP-1 R），这些化合物刺激胰岛素分泌，同时降低2型糖尿病（T2 DM）患者的血糖水平。用于治疗T2 DM的另一种治疗选择涉及施用二肽基肽酶-IV（DPP-IV）抑制剂（例如，Januvia，Galvus）.这些化合物减缓了肠道释放的GLP-1的代谢降解，从而显著提高了循环GLP-1的餐后水平。也存在刺激GLP-1分泌的研究性化合物，并且在这方面值得注意的进展是证明小分子GPR 119激动剂（例如，AR 231453）刺激L细胞GLP-1分泌，同时也直接刺激β细胞胰岛素释放。在这篇综述中，我们总结了目前已知的关于β细胞GLP-1 R的信号转导特性，因为它们与胰岛素分泌有关。重点是环AMP、蛋白激酶A和Epac 2介导的GLP-1调节ATP敏感性K+通道、电压依赖性K+通道、TRPM 2阳离子通道、细胞内Ca 2+释放通道和Ca 2+依赖性胞吐作用的作用。我们还讨论了新的证据，这些证据提供了一个概念框架，用于理解GLP-1 R激动剂用于治疗T2 DM时不太可能诱导低血糖的原因。
Insulin secretion from pancreatic β cells is stimulated by glucagon-like peptide-1 (GLP-1), a blood glucose-lowering hormone that is released from enteroendocrine L cells of the distal intestine after the ingestion of a meal. GLP-1 mimetics (e.g., Byetta) and GLP-1 analogs (e.g., Victoza) activate the β cell GLP-1 receptor (GLP-1R), and these compounds stimulate insulin secretion while also lowering levels of blood glucose in patients diagnosed with type 2 diabetes mellitus (T2DM). An additional therapeutic option for the treatment of T2DM involves the administration of dipeptidyl peptidase-IV (DPP-IV) inhibitors (e.g., Januvia, Galvus). These compounds slow metabolic degradation of intestinally released GLP-1, thereby raising post-prandial levels of circulating GLP-1 substantially. Investigational compounds that stimulate GLP-1 secretion also exist, and in this regard a noteworthy advance is the demonstration that small molecule GPR119 agonists (e.g., AR231453) stimulate L cell GLP-1 secretion while also directly stimulating β cell insulin release. In this review, we summarize what is currently known concerning the signal transduction properties of the β cell GLP-1R as they relate to insulin secretion. Emphasized are the cyclic AMP, protein kinase A, and Epac2 mediated actions of GLP-1 to regulate ATP-sensitive K+ channels, voltage-dependent K+ channels, TRPM2 cation channels, intracellular Ca2+ release channels, and Ca2+-dependent exocytosis. We also discuss new evidence that provides a conceptual framework with which to understand why GLP-1R agonists are less likely to induce hypoglycemia when they are administered for the treatment of T2DM.
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DOI：
10.1097/med.0b013e3283339051
发表时间：
2010-02-01
影响因子：
3.2
作者：
Asmar, Meena;Holst, Jens J.
通讯作者：
Holst, Jens J.
DOI：
10.1007/s00424-010-0835-z
发表时间：
2010-06
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Brixel LR;Monteilh-Zoller MK;Ingenbrandt CS;Fleig A;Penner R;Enklaar T;Zabel BU;Prawitt D
通讯作者：
Prawitt D
DOI：
10.1016/j.bbrc.2004.06.149
发表时间：
2004-08-11
影响因子：
3.1
作者：
Akiba, Y;Kato, S;Hibi, T
通讯作者：
Hibi, T
影响因子：
7.7
作者：
Barg, S;Eliasson, L;Rorsman, P
通讯作者：
Rorsman, P
影响因子：
4.8
作者：
Chepurny, Oleg G.;Leech, Colin A.;Holz, George G.
通讯作者：
Holz, George G.