Sener A, Welsh N, Malaisse-Lagae F, Kadiata M M, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Brussels, B-1070, Belgium.
Mol Genet Metab. 1998 Jun;64(2):135-47. doi: 10.1006/mgme.1998.2701.
The metabolism and metabolic effects of alpha-D-glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of alpha-D-glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of D-glucose in the islet cells. Second, the conversion of alpha-D-[5-3H]glucose pentaacetate to 3HOH and that of alpha-D-[U-14C]glucose pentaacetate to 14CO2 exceeded those found at an equimolar concentration (1.7 mM) of D-glucose and were both inhibited by 2-deoxy-D-glucose (16.7 mM). Last, the ester inhibited the catabolism of both exogenous D-glucose or endogenous fatty acids. Yet, an apparent dissociation between the metabolic and secretory responses to the ester was suggested by the failure of alpha-D-glucose pentaacetate to increase O2 uptake by the islets. Moreover, there were striking differences between the catabolism of the ester and that of unesterified D-glucose, such as a much higher intracellular D-glucose content and an insensitiveness to the inhibitory action of D-mannoheptulose in islets exposed to alpha-D-glucose pentaacetate. Likewise, the ratio between hexose oxidation and utilization was lower for alpha-D-glucose pentaacetate than for unesterified D-glucose in islets concomitantly exposed to the hexose and its ester. It is proposed, therefore, that the insulinotropic action of alpha-D-glucose pentaacetate, although probably linked to the intracellular generation of D-glucose from the ester, may not involve the same coupling process between metabolic and functional events as that currently implied in the process of glucose-stimulated insulin release.
在分离的大鼠胰岛中研究了α-D-葡萄糖五乙酸酯的代谢及其代谢效应。有几个发现与以下观点一致，即α-D-葡萄糖五乙酸酯的促胰岛素作用与其作为胰岛B细胞燃料的能力存在因果关系。首先，该酯被有效地摄取并水解，导致胰岛细胞中D-葡萄糖的积累。其次，α-D-[5-³H]葡萄糖五乙酸酯向³H₂O的转化以及α-D-[U-¹⁴C]葡萄糖五乙酸酯向¹⁴CO₂的转化超过了在等摩尔浓度（1.7 mM）的D-葡萄糖下的转化，并且两者均受到2-脱氧-D-葡萄糖（16.7 mM）的抑制。最后，该酯抑制了外源性D-葡萄糖或内源性脂肪酸的分解代谢。然而，α-D-葡萄糖五乙酸酯未能增加胰岛对氧气的摄取，这表明该酯的代谢反应和分泌反应之间存在明显的分离。此外，该酯的分解代谢与未酯化的D-葡萄糖的分解代谢之间存在显著差异，例如在暴露于α-D-葡萄糖五乙酸酯的胰岛中，细胞内D-葡萄糖含量更高，并且对D-甘露庚酮糖的抑制作用不敏感。同样，在同时暴露于己糖及其酯的胰岛中，α-D-葡萄糖五乙酸酯的己糖氧化与利用之间的比率低于未酯化的D-葡萄糖。因此，有人提出，α-D-葡萄糖五乙酸酯的促胰岛素作用虽然可能与该酯在细胞内生成D-葡萄糖有关，但可能不涉及与目前葡萄糖刺激胰岛素释放过程中所暗示的代谢和功能事件之间相同的偶联过程。
