Ladriere L, Kadiata M M, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Int J Mol Med. 1998 Jun;1(6):967-70. doi: 10.3892/ijmm.1.6.967.
D-mannoheptulose, which inhibits hexokinase isoenzymes in a predominantly competitive manner, has been found to decrease much more modestly D-glucose metabolism in pancreatic islets exposed to a low, as distinct from high, concentration of the hexose. In the present study, which aimed at investigating the factor(s) possibly responsible for such a phenomenon, a comparable situation was found to prevail in rat hepatocytes. However, when the hexaacetate ester of D-mannoheptulose was used instead of the unesterified heptose, the relative extent of inhibition of D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to 14C-labelled acidic metabolites was comparable in hepatocytes exposed to either 1.7 or 8.3 mM D-glucose. Moreover, at the low D-glucose level, the incorporation of 3-O-methyl-D-glucose (6.6 mM) into the incubation medium increased the inhibitory action of unesterified D-mannoheptulose upon D-glucose metabolism. These findings suggest that an insufficient uptake of the heptose accounts, in part at least, for its poor efficiency as inhibitor of D-glucose catabolism in liver, and presumably islet cells exposed to low concentrations of the hexose.
D-甘露庚酮糖主要以竞争性方式抑制己糖激酶同工酶，已发现它对暴露于低浓度（与高浓度不同）己糖的胰岛中D-葡萄糖代谢的降低幅度要小得多。在本研究中，旨在探究可能导致这种现象的因素，结果发现在大鼠肝细胞中也存在类似情况。然而，当使用D-甘露庚酮糖的六乙酸酯而非未酯化的庚糖时，在暴露于1.7 mM或8.3 mM D-葡萄糖的肝细胞中，D-[5-³H]葡萄糖利用和D-[U-¹⁴C]葡萄糖转化为¹⁴C标记酸性代谢物的相对抑制程度相当。此外，在低D-葡萄糖水平下，将3-O-甲基-D-葡萄糖（6.6 mM）加入孵育培养基中会增强未酯化D-甘露庚酮糖对D-葡萄糖代谢的抑制作用。这些发现表明，庚糖摄取不足至少部分解释了其作为肝脏中D-葡萄糖分解代谢抑制剂效率低下的原因，并且推测在暴露于低浓度己糖的胰岛细胞中也是如此。
