Pilkis S J, Claus T H, Johnson R A, Park C R
J Biol Chem. 1975 Aug 25;250(16):6328-36.
Glucagon can stimulate gluconeogenesis from 2 mM lactate nearly 4-fold in isolated liver cells from fed rats; exogenous cyclic adenosine 3':5'-monophosphate (cyclic AMP) is equally effective, but epinephrine can stimulate only 1.5-fold. Half-maximal effects are obtained with glucagon at 0.3 nM, cyclic AMP at 30 muM and epinephrine at 0.2 muM. Insulin reduces by 50% the stimulation by suboptimal concentrations of glucagon (0.5 nM). A half-maximal effect is obtained with 0.3 nM insulin (45 microunits/ml). Glucagon in the presence of theophylline (1 mM) causes a rapid rise and subsequent fall in intracellular cyclic AMP with a peak between 3 and 6 min. Some of the fall can be accounted for by loss of nucleotide into the medium. This efflux is suppressed by probenecid, suggesting the presence of a membrane transport mechanism for the cyclic nucleotide. Glucagon can raise intracellular cyclic AMP about 30-fold; a half-maximal effect is obtained with 1.5 nM hormone. Epinephrine (plus theophylline, 1 mM) can raise intracellular cyclic AMP about 2-fold; the peak elevation is reached in less than 1 min and declines during the next 15 min to near the basal level. Insulin (10 nM) does not lower the basal level of cyclic AMP within the hepatocyte, but suppresses by about 50% the rise in intracellular and total cyclic AMP caused by exposure to an intermediate concentration of glucagon. No inhibition of adenylate cyclase by insulin can be shown. Basal gluconeogenesis is not significantly depressed by calcium deficiency but stimulation by glucagon is reduced by 50%. Calcium deficiency does not reduce accumulation of cyclic AMP in response to glucagon but diminishes stimulation of gluconeogenesis by exogenous cyclic AMP. Glucagon has a rapid stimulatory effect on the flux of 45Ca2+ from medium to tissue.
胰高血糖素可使喂食大鼠分离肝细胞中由2 mM乳酸生成葡萄糖的糖异生作用增强近4倍；外源性环磷酸腺苷（cAMP）同样有效，但肾上腺素只能使其增强1.5倍。胰高血糖素在0.3 nM时、cAMP在30 μM时以及肾上腺素在0.2 μM时可产生半数最大效应。胰岛素可使次优浓度（0.5 nM）的胰高血糖素所引起的刺激作用降低50%。0.3 nM胰岛素（45微单位/毫升）可产生半数最大效应。在茶碱（1 mM）存在的情况下，胰高血糖素会使细胞内cAMP迅速升高，随后下降，峰值出现在3至6分钟之间。部分下降可归因于核苷酸向培养基中的流失。丙磺舒可抑制这种外流，提示存在一种环核苷酸的膜转运机制。胰高血糖素可使细胞内cAMP升高约30倍；1.5 nM激素可产生半数最大效应。肾上腺素（加1 mM茶碱）可使细胞内cAMP升高约2倍；峰值升高在不到1分钟内达到，并在接下来的15分钟内降至接近基础水平。胰岛素（10 nM）不会降低肝细胞内cAMP的基础水平，但可使暴露于中等浓度胰高血糖素时细胞内和总cAMP的升高抑制约50%。未显示胰岛素对腺苷酸环化酶有抑制作用。钙缺乏不会显著降低基础糖异生作用，但会使胰高血糖素的刺激作用降低50%。钙缺乏不会减少对胰高血糖素反应时cAMP的积累，但会减弱外源性cAMP对糖异生的刺激作用。胰高血糖素对45Ca2+从培养基向组织的通量有快速刺激作用。
