Imeglimin - A New Oral Anti-Diabetic that Targets the Three Key Defects of Type 2 Diabetes
Imeglimin - A New Oral Anti-Diabetic that Targets the Three Key Defects of Type 2 Diabetes
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DOI：
10.4172/2155-6156.1000126
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发表时间：
2011-05-01
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影响因子：
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通讯作者：
Bozec, Sophie
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文献类型：
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作者：
Fouqueray, Pascale;Leverve, Xavier;Bozec, Sophie
研究背景：这篇整理研究论文的目的是强调 imeglimin 的抗糖尿病作用和作用方式，imeglimin 是一类新的含四氢三嗪的口服抗糖尿病药物：glimins 中的第一个。 Imeglimin 作用于胰岛素抵抗器官（肝脏和肌肉）和胰腺 β 细胞（响应葡萄糖分泌胰岛素并防止细胞凋亡）。方法：本文报道的研究目的是提供有关 imeglimin 作用模式及其抗糖尿病作用的数据，证明它通过作用于该疾病的三个关键病理缺陷（即肝脏葡萄糖生成过多、骨骼肌外周葡萄糖摄取受损和胰岛素不足），成为治疗 2 型糖尿病的一种有前景的方法。结果：Imeglimin 以剂量依赖性方式显着降低 STZ 大鼠的空腹血糖浓度。与对照组 (9.83%) 相比，imeglimin (6.2%) 显着降低了 HbA1c (P< 0.01)。与对照组相比，150 mg.kg(-1)剂量的imeglimin显着改善了葡萄糖耐量（AUC分别为2,402 vs 3,449 mmol.L.h(-1)）。就其作用方式而言，伊格列明显着降低肝脏糖异生率，刺激肌肉葡萄糖摄取，诱导葡萄糖依赖性胰岛素分泌增强，并减少β细胞凋亡。结论：我们的研究发现，伊格列明独特地针对2型糖尿病的三个关键缺陷。与目前口服抗糖尿病药物相比，它可以提供更持久、持续的血糖控制，并且有可能在疾病连续体的任何阶段使用。 Imeglimin's potential for combination with other oral antidiabetics is also under investigation.
Study background: The objective of this collated research paper is to highlight the anti-diabetic effects and mode of action of imeglimin, the first in a new tetrahydrotriazine-containing class of oral anti-diabetic agents: the glimins. Imeglimin acts on both insulin resistant organs (liver and muscle) and pancreatic beta-cells (insulin secretion in response to glucose and protection against apoptosis).Methods: The aim of the investigations reported here is to present data on the mode of action of imeglimin and its anti-diabetic effects, demonstrating that it represents a promising treatment for type 2 diabetes by acting on the three key pathological defects of the disease, namely excessive hepatic glucose production, impaired peripheral glucose uptake by skeletal muscle, and insufficient insulin secretion.Results: Imeglimin significantly lowered fasting plasma glucose concentrations in a dose-dependent manner in STZ rats. HbA1c was significantly reduced (P< 0.01) by imeglimin (6.2%) compared with controls (9.83%). At a 150 mg.kg(-1) dose, imeglimin significantly improved glucose tolerance compared with controls (AUC 0-3h 2,402 vs 3,449 mmol.L.h(-1) respectively). With regards to its mode of action, imeglimin significantly decreased the rate of hepatic gluconeogenesis, stimulated muscle glucose uptake, induced a potentiation of glucose-dependent insulin secretion, and decreased beta-cell apoptosis.Conclusion: Our investigations found that imeglimin uniquely targets the three key defects of type 2 diabetes. It could provide more durable, sustained glycemic control than currently achieved with oral anti-diabetics and has the potential to be used at any stage in the disease continuum. Imeglimin's potential for combination with other oral antidiabetics is also under investigation.