Claus T H, Pilkis S J
Biochim Biophys Acta. 1976 Feb 24;421(2):246-62. doi: 10.1016/0304-4165(76)90291-9.
Insulin (10nM) completely suppressed the stimulation of gluconeogenesis from 2 mM lactate by low concentrations of glucagon (less than or equal to 0.1 nM) or cyclic AMP (less than or equal to 10 muM), but it had no effect on the basal rate of gluconeogenesis in hepatocyctes from fed rats. The effectiveness of insulin diminished as the concentration of these agonists increased, but insulin was able to suppress by 40% the stimulation by a maximally effective concentration of epinephrine (1 muM). The response to glucagon, epinephrine, or insulin was not dependent upon protein synthesis as cycloheximide did not alter their effects. Insulin also suppressed the stimulation by isoproterenol of cyclic GMP. These data are the first demonstration of insulin antagonism to the stimulation of gluconeogenesis by catecholamines. Insulin reduced cyclic AMP levels which had been elevated by low concentrations of glucagon or by 1 muM epinephrine. This supports the hypothesis that the action of insulin to inhibit gluconeogenesis is mediated by the lowering of cyclic AMP levels. However, evidence is presented which indicates that insulin is able to suppress the stimulation of gluconeogenesis by glucagon or epinephrine under conditions where either the agonists or insulin had no measurable effect on cyclic AMP levels. Insulin reduced the glucagon stimulation of gluconeogenesis whether or not extracellular Ca2+ were present, even though insulin only lowered cyclic AMP levels in their presence. Insulin also reduced the stimulation by epinephrine plus propranolol where no significant changes in cyclic AMP were observed without or with insulin. In addition, insulin suppressed gluconeogenesis in cells that had been preincubated with epinephrine for 20 min, even though the cyclic AMP levels had returned to near basal values and were unaffected by insulin. Thus insulin may not need to lower cyclic AMP levels in order to suppress gluconeogenesis.
胰岛素（10纳摩尔）完全抑制了低浓度胰高血糖素（小于或等于0.1纳摩尔）或环磷酸腺苷（小于或等于10微摩尔）对2毫摩尔乳酸糖异生的刺激作用，但对喂食大鼠肝细胞的基础糖异生速率没有影响。随着这些激动剂浓度的增加，胰岛素的有效性降低，但胰岛素能够抑制最大有效浓度肾上腺素（1微摩尔）刺激的40%。对胰高血糖素、肾上腺素或胰岛素的反应不依赖于蛋白质合成，因为放线菌酮不会改变它们的作用。胰岛素还抑制了异丙肾上腺素对环磷酸鸟苷的刺激作用。这些数据首次证明了胰岛素对儿茶酚胺刺激糖异生的拮抗作用。胰岛素降低了低浓度胰高血糖素或1微摩尔肾上腺素升高的环磷酸腺苷水平。这支持了胰岛素抑制糖异生的作用是通过降低环磷酸腺苷水平介导的这一假设。然而，有证据表明，在激动剂或胰岛素对环磷酸腺苷水平没有可测量影响的情况下，胰岛素能够抑制胰高血糖素或肾上腺素对糖异生的刺激作用。无论细胞外是否存在钙离子，胰岛素都能降低胰高血糖素对糖异生的刺激作用，尽管胰岛素仅在钙离子存在时才降低环磷酸腺苷水平。胰岛素还降低了肾上腺素加普萘洛尔的刺激作用，在有无胰岛素的情况下，环磷酸腺苷均未观察到显著变化。此外，胰岛素抑制了预先用肾上腺素预孵育20分钟的细胞中的糖异生，尽管环磷酸腺苷水平已恢复到接近基础值且不受胰岛素影响。因此，胰岛素可能不需要降低环磷酸腺苷水平来抑制糖异生。
