Yu B, Pugazhenthi S, Khandelwal R L
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Biochem Pharmacol. 1994 Aug 30;48(5):949-54. doi: 10.1016/0006-2952(94)90365-4.
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 microM) 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 microM) 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.
在正常和糖尿病肝细胞中研究了葡萄糖和胰高血糖素对二甲双胍抗糖异生作用的影响。与喂食动物的肝细胞相比，禁食正常大鼠的肝细胞中由乳酸生成葡萄糖的量增加了88%。糖尿病分别使禁食和喂食条件下的肝脏糖异生增加了3.5倍和2.1倍。二甲双胍（250微摩尔）使喂食大鼠的正常肝细胞和糖尿病肝细胞中的葡萄糖生成分别抑制了37%和30%。随着培养基中葡萄糖浓度的增加，这种药物的效果更明显（高达67%）。在体外，葡萄糖显著增强了二甲双胍对糖异生的胰岛素作用的增强作用（P<0.01至0.001）。二甲双胍（75 - 250微摩尔）在正常（32 - 68%）和糖尿病（8 - 46%）肝细胞中，在最佳浓度下也能抵消胰高血糖素的作用。本研究结果表明：（i）二甲双胍的抗糖异生作用在体内和体外均因葡萄糖而增强；（ii）二甲双胍对胰高血糖素诱导的糖异生的抑制作用可能在其对糖尿病患者的降糖作用中发挥作用。
