Differential hypoglycemic effect of 2,5-anhydro-D-mannitol, a putative gluconeogenesis inhibitor, in genetically diabetic (db/db) and streptozotocin-induced diabetic mice.
Differential hypoglycemic effect of 2,5-anhydro-D-mannitol, a putative gluconeogenesis inhibitor, in genetically diabetic (db/db) and streptozotocin-induced diabetic mice.
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2,5-脱水-D-甘露醇（一种假定的糖异生抑制剂）对遗传性糖尿病 (db/db) 和链脲佐菌素诱导的糖尿病小鼠的不同降血糖作用。
DOI：
10.1254/jjp.66.331
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
I. Yamaguchi
中科院分区：
文献类型：
--
作者：
H. Kodama;M. Fujita;I. Yamaguchi
2，5-脱水-D-甘露醇(AM)是一种潜在的糖异生抑制物，可完全逆转遗传性糖尿病(db/db)小鼠的高血糖，与对照组+/+小鼠相比，db/db小鼠表现出高胰岛素血症和肝糖异生酶(葡萄糖-6-磷酸酶(G-6-Pase)和果糖-1，6-二磷酸酶(F-1，6-DPase))活性。相反，AM只能部分逆转链脲佐菌素(STZ)处理的+/+小鼠的高血糖，其中肝脏糖异生酶的活性与db/db小鼠相同程度地增强，而血液胰岛素水平则受到抑制。在db/db小鼠中，链脲佐菌素降低高胰岛素血症，夸大高血糖和肝糖异生酶的活性，使AM的降血糖作用大大减弱。在+/+、STZ处理的+/+和STZ处理的db/db小鼠中，不仅AM的剂量-反应曲线，而且在给药320 mg/kg后血糖水平的时程(以治疗前的百分比表示)几乎相同。在STZ治疗的+/+小鼠中，胰岛素(320微克/公斤)和AM(320 mg/公斤)联合治疗引起的低血糖比AM或胰岛素单独引起的低血糖更严重。另一方面，对纯化的F-1，6-DPase的体外研究表明，磷酸化的AM(AM-1，6-二磷酸)而不是AM本身抑制了糖异生酶的活性。这些结果表明，糖异生的抑制至少部分是AM的降血糖活性的原因AM在被胰岛素依赖的机制磷酸化后，似乎抑制了肝糖异生酶的活性。
2,5-Anhydro-D-mannitol (AM), a putative gluconeogenesis inhibitor, completely reversed the hyperglycemia in genetically diabetic (db/db) mice that exhibited hyperinsulinemia and enhanced hepatic gluconeogenic enzyme (glucose-6-phosphatase (G-6-Pase) and fructose-1,6-diphosphatase (F-1,6-DPase)) activities compared with the control +/+ mice. In contrast, AM only partially reversed the hyperglycemia of streptozotocin (STZ)-treated +/+ mice in which the hepatic gluconeogenic enzyme activities were enhanced to the same degree as in the db/db mice, whereas the blood insulin level was depressed. In the db/db mice, the STZ-treatment attenuated the hyperinsulinemia and exaggerated the hyperglycemia as well as the hepatic gluconeogenic enzyme activities, and it greatly reduced the hypoglycemic action of AM. Not only the dose-response curve of AM but also the time-course of the blood glucose level (expressed as % of pre-treatment value) following 320 mg/kg of AM were almost identical between +/+, STZ-treated +/+ and STZ-treated db/db mice. In the STZ-treated +/+ mice, a combination treatment of insulin (320 micrograms/kg) with AM (320 mg/kg) caused hypoglycemia that was greater than that induced by AM or insulin alone. On the other hand, in vitro studies with purified F-1,6-DPase revealed that phosphorylated AM (AM-1,6-diphosphate) but not AM itself inhibited the gluconeogenic enzyme activities. These results suggest that inhibition of gluconeogenesis is responsible, at least in part, for the hypoglycemic activity of AM. AM appears to inhibit hepatic gluconeogenic enzyme activities after being phosphorylated by an insulin-dependent mechanism.
2,5-脱水-D-甘露醇抑制糖异生和糖原分解。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hanson,RL;Ho,RS;Wiseberg,JJ;Simpson,R;Younathan,ES;Blair,JB
通讯作者：
Blair,JB
DOI：
10.1016/s0021-9258(17)42964-4
发表时间：
1984-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Riquelme;M. E. Wernette-Hammond;N. Kneer;H. Lardy
通讯作者：
P. Riquelme;M. E. Wernette-Hammond;N. Kneer;H. Lardy
2,5-脱水-D-甘露醇调节碳水化合物代谢。
DOI：
10.1073/pnas.80.14.4301
发表时间：
1983
影响因子：
11.1
作者：
Riquelme,PT;Wernette-Hammond,ME;Kneer,NM;Lardy,HA
通讯作者：
Lardy,HA