The role of peroxisome proliferator-activated receptor γ in pancreatic β cell function and survival: therapeutic implications for the treatment of type 2 diabetes mellitus.
The role of peroxisome proliferator-activated receptor γ in pancreatic β cell function and survival: therapeutic implications for the treatment of type 2 diabetes mellitus.
复制标题
过氧化物酶体增殖物激活受体γ在胰腺β细胞功能与存活中的作用：对2型糖尿病治疗的意义
DOI：
10.1111/j.1463-1326.2010.01299.x
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Evans-Molina C
中科院分区：
文献类型：
--
作者：
Gupta D;Kono T;Evans-Molina C
2型糖尿病的发病机制涉及外周胰岛素抵抗和胰岛β细胞分泌胰岛素功能障碍。目前，有大量的研究集中在描绘2型糖尿病胰腺β细胞功能障碍的病因。然而，仍然存在未满足的临床需求，以建立强调在风险和受影响个体中保留胰腺β细胞功能的治疗指南和策略。噻唑烷二酮类药物是批准用于2型糖尿病的口服活性药物，可作为核激素受体PPAR-γ的激动剂。这些药物改善胰岛素敏感性，但在β细胞内对PPAR-γ作用的认识也越来越高。已显示PPAR-γ直接调节参与葡萄糖感知、胰岛素分泌和胰岛素基因转录的关键β细胞基因。此外，药理学PPAR-γ活化已显示保护免受葡萄糖、脂质、细胞因子和胰岛淀粉样多肽（IAPP）诱导的许多应激途径的活化。本文将综述2型糖尿病患者中PPAR-γ激活维持β细胞功能和存活的机制，并重点介绍该领域目前存在的一些争议。
The pathogenesis of type 2 diabetes mellitus involves both peripheral insulin resistance and dysfunctional insulin secretion from the pancreatic β cell. Currently, there is intense research focus on delineating the etiologies of pancreatic β cell dysfunction in type 2 diabetes. However, there remains an unmet clinical need to establish therapeutic guidelines and strategies that emphasize the preservation of pancreatic β cell function in at-risk and affected individuals. Thiazolidinediones are orally active agents approved for use in type 2 diabetes and act as agonists of the nuclear hormone receptor PPAR-γ. These drugs improve insulin sensitivity, but there is also a growing appreciation of PPAR-γ actions within the β cell. PPAR-γ has been shown to regulate directly key β cell genes involved in glucose sensing, insulin secretion and insulin gene transcription. Further, pharmacologic PPAR-γ activation has been shown to protect against glucose-, lipid-, cytokine- and islet amyloid polypeptide (lAPP)-induced activation of numerous stress pathways. This article will review the mechanisms by which PPAR-γ activation acts to maintain β cell function and survival in type 2 diabetes mellitus and highlight some of the current controversies in this field.
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