Wernette-Hammond M E, Lardy H A
Diabetes. 1985 Aug;34(8):767-73. doi: 10.2337/diab.34.8.767.
Hepatocytes from fasted, alloxan-diabetic rats were incubated in the absence of gluconeogenic substrates to deplete residual glycogen stores. Glucose production from lactate and pyruvate was enhanced in cells from diabetic rats relative to similarly treated hepatocytes from fasted, nondiabetic control rats. Gluconeogenesis from dihydroxyacetone, fructose, or glycerol was not increased but the formation of lactate plus pyruvate from dihydroxyacetone was decreased. The stimulation of gluconeogenesis by exogenous fatty acids was decreased by diabetes. The rates of gluconeogenesis in the presence of lactate plus pyruvate plus oleate were equal in hepatocytes from diabetic and control rats and indicate that the maximal rate of gluconeogenesis was not increased. With lactate plus pyruvate as substrates, stimulation of gluconeogenesis by norepinephrine or dibutyryl-cAMP was not altered by diabetes. The catecholamine stimulation of gluconeogenesis from glycerol also was unaffected. In contrast, diabetes decreased the maximal stimulation of gluconeogenesis from dihydroxyacetone by dibutyryl-cAMP, glucagon, or norepinephrine and this decrease was proportional to the decreased production of lactate plus pyruvate. The concentrations of glucagon or norepinephrine required for half-maximal stimulation were not altered by diabetes. Thus, the hormonal stimulation of gluconeogenesis from dihydroxyacetone is decreased by diabetes, probably because of decreased pyruvate kinase activity, but the interaction of glucagon and norepinephrine with hepatocytes and the subsequent stimulation of gluconeogenesis from physiologic substrates is not impaired.
将禁食的四氧嘧啶糖尿病大鼠的肝细胞在缺乏糖异生底物的情况下孵育，以耗尽残余的糖原储备。与同样处理的禁食非糖尿病对照大鼠的肝细胞相比，糖尿病大鼠细胞中由乳酸和丙酮酸生成葡萄糖的能力增强。由二羟基丙酮、果糖或甘油进行的糖异生没有增加，但由二羟基丙酮生成乳酸加丙酮酸的过程减少。糖尿病降低了外源性脂肪酸对糖异生的刺激作用。在存在乳酸加丙酮酸加油酸的情况下，糖尿病大鼠和对照大鼠肝细胞中的糖异生速率相等，这表明糖异生的最大速率没有增加。以乳酸加丙酮酸为底物时，去甲肾上腺素或二丁酰环磷腺苷对糖异生的刺激作用不受糖尿病影响。儿茶酚胺对由甘油进行的糖异生的刺激作用也未受影响。相比之下，糖尿病降低了二丁酰环磷腺苷、胰高血糖素或去甲肾上腺素对由二羟基丙酮进行的糖异生的最大刺激作用，且这种降低与乳酸加丙酮酸生成量的减少成比例。半最大刺激所需的胰高血糖素或去甲肾上腺素浓度不受糖尿病影响。因此，糖尿病降低了由二羟基丙酮进行的糖异生的激素刺激作用，可能是由于丙酮酸激酶活性降低，但胰高血糖素和去甲肾上腺素与肝细胞的相互作用以及随后对生理性底物进行的糖异生的刺激作用并未受损。
