Regulation of carbohydrate metabolism by 2,5-anhydro-D-mannitol.
Regulation of carbohydrate metabolism by 2,5-anhydro-D-mannitol.
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2,5-脱水-D-甘露醇调节碳水化合物代谢。
DOI：
10.1073/pnas.80.14.4301
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发表时间：
1983
影响因子：
11.1
通讯作者：
Lardy,HA
中科院分区：
文献类型：
--
作者：
Riquelme,PT;Wernette-Hammond,ME;Kneer,NM;Lardy,HA
在从禁食大鼠中分离的肝细胞中，2，5-脱水甘露醇抑制乳酸加丙酮酸以及作为磷酸丙糖进入促肝细胞生成途径的底物的促肝细胞生成。然而，这种果糖类似物对木糖醇的代谢没有影响，木糖醇是一种主要作为果糖6-磷酸进入途径的底物。异源生成对2，5-脱水甘露醇的敏感性取决于代谢的底物; 50%抑制所需的2，5-脱水甘露醇浓度按以下顺序增加：乳酸加丙酮酸低于二羟丙酮低于甘油低于山梨醇低于果糖。2，5-脱水甘露醇对二羟基丙酮的糖酵解的抑制伴随着乳酸盐形成的增加和糖酵解代谢物模式的两种不同的交叉-即，丙酮酸浓度增加，磷酸烯醇丙酮酸减少，果糖-1，6-二磷酸浓度增加，果糖6-磷酸变化不大。此外，2，5-脱水甘露醇阻断胰高血糖素刺激胰异生和抑制二羟基丙酮产生乳酸的能力。2，5-脱水甘露醇可降低肝细胞中2，6-二磷酸果糖的含量;因此，果糖类似物的作用不由2，6-二磷酸果糖（一种天然存在的变构调节剂）介导。2，5-脱水甘露醇也抑制从禁食糖尿病大鼠分离的肝细胞中的肝细胞生成，但需要更高浓度的类似物。
In hepatocytes isolated from fasted rats, 2,5-anhydromannitol inhibits gluconeogenesis from lactate plus pyruvate and from substrates that enter the gluconeogenic pathway as triose phosphate. This fructose analog has no effect, however, on gluconeogenesis from xylitol, a substrate that enters the pathway primarily as fructose 6-phosphate. The sensitivity of gluconeogenesis to 2,5-anhydromannitol depends on the substrate metabolized; concentrations of 2,5-anhydromannitol required for 50% inhibition increase in the order lactate plus pyruvate less than dihydroxyacetone less than glycerol less than sorbitol less than fructose. The inhibition by 2,5-anhydromannitol of gluconeogenesis from dihydroxyacetone is accompanied by an increase in lactate formation and by two distinct crossovers in gluconeogenic-glycolytic metabolite patterns-i.e., increases in pyruvate concentrations with decreases in phosphoenolpyruvate and increases in fructose-1,6-bisphosphate concentrations with little change in fructose 6-phosphate. In addition, 2,5-anhydromannitol blocks the ability of glucagon to stimulate gluconeogenesis and inhibit lactate production from dihydroxyacetone. 2,5-Anhydromannitol decreases cellular fructose 2,6-bisphosphate content in hepatocytes; therefore the effects of the fructose analog are not mediated by fructose 2,6-bisphosphate, a naturally occurring allosteric regulator. 2,5-Anhydromannitol also inhibits gluconeogenesis in hepatocytes isolated from fasted diabetic rats, but higher concentrations of the analog are required.