Ayvaz G, Sener A, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Res Commun Mol Pathol Pharmacol. 1999 Jan;103(1):83-90.
The pentaacetate ester of alpha-D-glucose was recently introduced as a new insulin secretagogue. Its insulinotropic action appears mainly attributable to the catabolism of its hexose moiety in islet cells, but a direct effect of the ester itself upon a receptor apparently displaying analogy with that involved in the recognition of bitter agents by taste buds may also be operative. In the present study, the secretory response of rat isolated pancreatic islets to alpha-D-glucose pentaacetate (1.7 mM) was found to be preserved, except in the absence of any other exogenous nutrient, when the extracellular pH was raised from about 7.4 to 8.0. Inversely, however, when the extracellular pH was lowered to about 7.0, alpha-D-glucose pentaacetate inhibited both basal and D-glucose- or L-leucine-stimulated insulin output. These findings are interpreted to support a dual mode of action of alpha-D-glucose pentaacetate upon insulin secretion, a lowering of extracellular pH revealing a negative component of the islet B-cells functional response to such a monosaccharide ester.
α-D-葡萄糖五乙酸酯最近作为一种新型胰岛素促分泌剂被引入。其促胰岛素作用似乎主要归因于其己糖部分在胰岛细胞中的分解代谢，但该酯本身对一种受体的直接作用（该受体显然与味蕾识别苦味剂所涉及的受体类似）也可能起作用。在本研究中，发现当细胞外pH从约7.4升高到8.0时，除了没有任何其他外源性营养物质的情况外，大鼠分离的胰岛对α-D-葡萄糖五乙酸酯（1.7 mM）的分泌反应得以保留。然而，相反地，当细胞外pH降低到约7.0时，α-D-葡萄糖五乙酸酯会抑制基础以及D-葡萄糖或L-亮氨酸刺激的胰岛素分泌。这些发现被解释为支持α-D-葡萄糖五乙酸酯对胰岛素分泌的双重作用模式，细胞外pH的降低揭示了胰岛B细胞对这种单糖酯功能反应的负性成分。
