Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice.
Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice.
复制标题
胰高血糖素和胰岛素对正常和遗传性肥胖 (ob/ob) 小鼠灌注肝脏中脂肪酸合成和糖原降解的影响。
作者：
G. Y. Ma;C. Gove;D. Hems
1.研究了激素对小鼠灌注肝脏中糖原代谢和脂肪酸合成的快速影响。 2.在持续2小时的正常小鼠肝脏灌注中，连续剂量的胰高血糖素，每次产生的浓度为10(-10)或10(-9)M，抑制脂肪酸和胆固醇的合成。在持续40--50分钟的灌注中，其中培养基不循环，仅在胰高血糖素浓度大于10(-9)M时观察到脂肪酸合成的抑制。该浓度比刺激糖原分解所需的浓度高约两个数量级。添加胰高血糖素(10(-9)或10(-10)M)后10或20分钟进行测定，胰高血糖素不抑制乙酰辅酶A羧化酶的活性。有人提出，胰高血糖素对肝脂肪酸生物合成的作用可能是继糖原消耗之后的继发作用。胰岛素可以阻止胰高血糖素 (10(-10)M) 对糖原分解的作用，但不能阻止加压素的作用。 3. 遗传性肥胖（ob/ob）小鼠的肝脏并未表现出对胰高血糖素反应的脂质生物合成的显着抑制，尽管糖原分解正常加速。这种对胰高血糖素作用的抵抗不会因食物匮乏而逆转。肥胖小鼠的肝脏对胰高血糖素刺激的糖原分解的胰岛素抵抗表现出抵抗力，这种抵抗力可以通过部分食物剥夺来逆转。
1. Rapid effects of hormones on glycogen metabolism and fatty acid synthesis in the perfused liver of the mouse were studied. 2. In perfusions lasting 2h, of livers from normal mice, glucagon in successive doses, each producing concentrations of 10(-10) or 10(-9)M, inhibited fatty acid and cholesterol synthesis. In perfusions lasting 40--50 min, in which medium was not recycled, inhibition of fatty acid synthesis was only observed with glucagon at concentrations greater than 10(-9)M. This concentration was about two orders of magnitude higher than that required for the stimulation of glycogen breakdown. Glucagon did not inhibit the activity of acetyl-CoA carboxylase, assayed 10 or 20 min after addition of glucagon (10(-9) or 10(-10)M). It is proposed that the action of glucagon on hepatic fatty acid biosynthesis could be secondary in time to depletion of glycogen. Insulin prevented the effect of glucagon (10(-10)M) on glycogenolysis, but not that of vasopressin. 3. Livers of genetically obese (ob/ob) mice did not show significant inhibition of lipid biosynthesis in response to glucagon, although there was normal acceleration of glycogen breakdown. This resistance to glucagon action was not reversed by food deprivation. Livers of obese mice exhibited resistance to the counteraction by insulin of glucagon-stimulated glycogenolysis, which was reversible by partial food deprivation.