Sener A, Kadiata M M, Ladrière L, Malaisse W J
Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, Belgium.
Endocrine. 1997 Oct;7(2):151-5. doi: 10.1007/BF02778136.
Succinic acid esters are currently under investigation as possible insulinotropic tools in the treatment of noninsulin-dependent diabetes mellitus. The present article introduces three novel nutrient esters and aims mainly to explore, in both normal and GK rats, the secretory response to such esters when tested alone or in combination. It documents that in pancreatic islets from normal rats, methyl acetate (10 mM), which fails to augment basal insulin output, potentiates the secretory response to succinate dimethyl ester (also 10 mM). It also reveals that alpha-D-glucose pentaacetate (alpha GPA) (1.7 mM) stimulates insulin release in the absence of any other exogenous nutrient and even more so in the presence of succinate methyl ester. Moreover, the methyl esters of succinic acid (10 mM), when used together with either methyl acetate or alpha GPA, provoked insulin secretion in islets from diabetic GK rats incubated in the absence of D-glucose, although no significant secretory response of such islets could be detected when each of these agents was tested separately. These findings thus draw attention to the insulinotropic potential in type 2 diabetes of selected combinations of nutrient esters, including a D-glucose ester presumably able to enter into islet cells without requiring the intervention of a hexose carrier.
琥珀酸酯目前正在作为治疗非胰岛素依赖型糖尿病的潜在促胰岛素分泌工具进行研究。本文介绍了三种新型营养酯，主要目的是在正常大鼠和GK大鼠中，探索单独或联合测试时对这些酯的分泌反应。研究表明，在正常大鼠的胰岛中，乙酸甲酯（10 mM）虽不能增加基础胰岛素分泌量，但能增强对二甲基琥珀酸酯（也是10 mM）的分泌反应。研究还表明，α-D-葡萄糖五乙酸酯（α GPA）（1.7 mM）在没有任何其他外源营养物质的情况下能刺激胰岛素释放，在有甲基琥珀酸酯存在时刺激作用更强。此外，琥珀酸甲酯（10 mM）与乙酸甲酯或α GPA一起使用时，能在无糖培养的糖尿病GK大鼠胰岛中引发胰岛素分泌，不过单独测试这些试剂时，未检测到此类胰岛有明显的分泌反应。因此，这些发现引起了人们对特定营养酯组合在2型糖尿病中的促胰岛素分泌潜力的关注，其中包括一种可能无需己糖载体干预就能进入胰岛细胞的D-葡萄糖酯。
