EFFECTS OF METFORMIN ON GLUCOSE AND GLUCAGON REGULATED GLUCONEOGENESIS IN CULTURED NORMAL AND DIABETIC HEPATOCYTES
EFFECTS OF METFORMIN ON GLUCOSE AND GLUCAGON REGULATED GLUCONEOGENESIS IN CULTURED NORMAL AND DIABETIC HEPATOCYTES
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DOI：
10.1016/0006-2952(94)90365-4
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发表时间：
1994-08-30
影响因子：
5.8
通讯作者：
KHANDELWAL, RL
中科院分区：
文献类型：
--
作者：
YU, B;PUGAZHENTHI, S;KHANDELWAL, RL
研究了葡萄糖和胰高血糖素对正常和糖尿病肝细胞二甲双胍抗糖异生作用的影响。与喂食动物肝细胞相比，禁食的正常大鼠肝细胞乳酸产生的葡萄糖增加了88%。糖尿病导致空腹和进食条件下肝脏糖异生分别增加3.5倍和2.1倍。二甲双胍（250 μ M）对正常大鼠和糖尿病大鼠肝细胞的葡萄糖产生抑制作用分别为37%和30%。随着培养基中葡萄糖浓度的增加，该药物更有效（高达67%）。二甲双胍增强胰岛素对体外葡萄糖异生的作用显著升高（P < 0.01 ~ 0.001）。二甲双胍（75-250 μ M）在正常（32-68%）和糖尿病（8-46%）肝细胞中也能抵消胰高血糖素在最佳浓度下的影响。本研究结果表明：(1)体内和体外实验中，葡萄糖可增强二甲双胍的抗糖异生作用；（ii）二甲双胍抑制胰高血糖素诱导的糖异生可能在其降糖作用中发挥作用。
The effects of glucose and glucagon on the anti-gluconeogenic action of metformin were investigated in normal and diabetic hepatocytes. Glucose production from lactate was elevated by 88% in hepatocytes from fasted normal rats compared with hepatocytes from fed animals. Diabetes caused 3.5- and 2.1-fold increases in hepatic gluconeogenesis under fasting and fed conditions, respectively. Metformin (250 mu M) suppressed glucose production by 37% in normal and by 30% in diabetic hepatocytes from fed rats. This drug was more effective (up to 67%) with increasing concentrations of glucose in the medium. Potentiation by metformin of insulin action on gluconeogenesis was elevated significantly (P < 0.01 to 0.001) by glucose in vitro. Metformin (75-250 mu M) also counteracted the effects of glucagon at optimal concentrations in normal (32-68%) as well as diabetic (8-46%) hepatocytes. The findings of this study indicate that (i) the anti-gluconeogenic effect of metformin is enhanced by glucose in vivo and in vitro; and (ii) the suppression of glucagon-induced gluconeogenesis by metformin could play a role in its glucose-lowering effects in diabetic conditions.