Malaisse W J, Kadiata M M
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Int J Mol Med. 1998 Jul;2(1):95-8. doi: 10.3892/ijmm.2.1.95.
The polyacetate esters of certain non-nutrient monosaccharides, such as L-glucose and 2-deoxy-D-glucose, were recently reported to display positive insulinotropic action and, hence, proposed as possible tools for stimulation of insulin release in non-insulin-dependent diabetes. In the present study, the secretory response to four carbohydrate esters was compared in islets of both normal and hereditary diabetic Goto-Kakizaki rats. Three major findings are documented. First, in islets exposed to the dimethyl ester of succinic acid (10.0 mmol/l), D-mannoheptulose hexaacetate (1.7 mmol/l) was found to stimulate insulin release in both normal and diabetic rats. Second, relative to the control value recorded in the sole presence of the succinic acid ester, the increments in insulin output evoked by D-mannoheptulose hexaacetate, alpha-L-glucose pentaacetate and beta-D-glucose pentaacetate (all 1.7 mmol/l) were not lower and, on occasion, even higher in diabetic rats than in control animals. Last, the sole exception to such a rule was encountered in islets exposed to beta-L-glucose pentaacetate, in which case the hexose moiety of the ester might mimic the inhibitory effect of alpha-D-glucopyranose upon phosphorylase a-catalyzed glycogenolysis in islets from diabetic rats. These findings reinforce the concept that the insulinotropic action of monosaccharide esters is not solely attributable to the catabolism of their carbohydrate moiety but also to a direct effect of the esters themselves upon a yet unidentified receptor system. They also provide further support to the possible use of the esters of non-nutrient monosaccharides as insulinotropic tools in type-2 diabetes.
最近有报道称，某些非营养性单糖的聚乙酸酯，如L-葡萄糖和2-脱氧-D-葡萄糖，具有促胰岛素分泌作用，因此被提议作为刺激非胰岛素依赖型糖尿病患者胰岛素释放的可能工具。在本研究中，比较了正常和遗传性糖尿病Goto-Kakizaki大鼠胰岛对四种碳水化合物酯的分泌反应。记录了三个主要发现。第一，在暴露于琥珀酸二甲酯（10.0 mmol/l）的胰岛中，发现D-甘露庚酮糖六乙酸酯（1.7 mmol/l）可刺激正常和糖尿病大鼠的胰岛素释放。第二，相对于仅存在琥珀酸酯时记录的对照值，D-甘露庚酮糖六乙酸酯、α-L-葡萄糖五乙酸酯和β-D-葡萄糖五乙酸酯（均为1.7 mmol/l）引起的胰岛素分泌增加在糖尿病大鼠中并不低于对照动物，有时甚至更高。最后，在暴露于β-L-葡萄糖五乙酸酯的胰岛中遇到了这一规则的唯一例外，在这种情况下，酯的己糖部分可能模拟了α-D-吡喃葡萄糖对糖尿病大鼠胰岛中磷酸化酶a催化的糖原分解的抑制作用。这些发现强化了这样一种概念，即单糖酯的促胰岛素分泌作用不仅归因于其碳水化合物部分的分解代谢，还归因于酯本身对尚未确定的受体系统的直接作用。它们还进一步支持了非营养性单糖酯可能作为2型糖尿病促胰岛素分泌工具的用途。
