In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose.
In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose.
复制标题
体外逆转大鼠肝脏代谢的禁食状态。
DOI：
10.1172/jci110230
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
McGarry,JD
中科院分区：
文献类型：
--
作者：
Boyd,ME;Albright,EB;Foster,DW;McGarry,JD
进行研究以确定大鼠肝脏碳水化合物和脂质代谢的方向是否可以在体外同时从“禁食”转变为“进食”。当在适当条件下孵育2小时时，禁食动物的肝细胞可被诱导以体内速率合成糖原。伴随着组织丙二酰辅酶A水平的显著升高，脂肪酸合成的加速，脂肪酸氧化和生酮的抑制。与一些实验室的报告一致，但与流行的观点相反，葡萄糖不能被细胞有效地吸收，因此是糖原合成或脂肪生成的不良底物。糖原形成的最佳前体是果糖，而乳酸（丙酮酸）在脂肪生成中最有效。在这两种情况下，除了葡萄糖的促血管生成的底物是刺激性的，最高的利率得到进一步列入谷氨酰胺。胰岛素既不是必需的，也不刺激，糖原沉积或脂肪酸合成在有利的底物条件下。生理浓度的胰高血糖素抑制糖原形成和脂肪酸合成。胰岛素在其浓度曲线的次最大范围内容易逆转胰高血糖素的作用。得出以下结论。首先，肝脏碳水化合物和脂质代谢的禁食至进食过渡可以在体外在与体内操作相似的时间范围内完成。第二，逆转似乎是一种底物驱动的现象，因为不需要胰岛素。第三，除非一种未鉴定的因子（在进食期间存在于门静脉血中）促进肝脏对葡萄糖的摄取，否则葡萄糖似乎不太可能是体内肝糖原或脂肪合成的直接前体。在这两个过程中的主要底物的可能候选者是乳酸盐，其通过小肠和外周组织由葡萄糖快速形成。果糖和氨基酸也可能起作用。第四，在体内肝脏代谢的禁食状态的逆转中对胰岛素的需求可以通过其抵消胰高血糖素的分解代谢作用的能力来最好地解释。
Studies were conducted to determine whether the direction of hepatic carbohydrate and lipid metabolism in the rat could be switched simultaneously from a "fasted" to a "fed" profile in vitro. When incubated for 2 h under appropriate conditions hepatocytes from fasted animals could be induced to synthesize glycogen at in vivo rates. There was concomitant marked elevation of the tissue malonyl-coenzyme A level, acceleration of fatty acid synthesis, and suppression of fatty acid oxidation and ketogenesis. In agreement with reports from some laboratories, but contrary to popular belief, glucose was not taken up efficiently by the cells and was thus a poor substrate for eigher glycogen synthesis or lipogenesis. The best precursor for glycogen formation was fructose, whereas lactate (pyruvate) was most efficient in lipogenesis. In both case the addition of glucose to the gluconeogenic substrates was stimulatory, the highest rates being obtained with the further inclusion of glutamine. Insulin was neither necessary for, nor did it stimulate, glycogen deposition or fatty acid synthesis under favorable substrate conditions. Glucagon at physiological concentrations inhibited both glycogen formation and fatty acid synthesis. Insulin readily reversed the effects of glucagon in the submaximal range of its concentration curve. The following conclusions were drawn. First, the fasted-to-fed transition of hepatic carbohydrate and lipid metabolism can be accomplished in vitro over a time frame similar to that operative in vivo. Second, reversal appears to be a substrate-driven phenomenon, in that insulin is not required. Third, unless an unidentified factor (present in protal blood during feeding) facilitates the uptake of glucose by liver it seems unlikely that glucose is the immediate precursor for liver glycogen or fat synthesis in vivo. A likely candidate for the primary substrate in both processes is lactate, which is rapidly formed from glucose by the small intestine and peripheral tissues. Fructose and amino acids may also contribute. Fourth, the requirement for insulin in the reversal of the fasting state of liver metabolism in vivo can best be explained by its ability to offset the catabolic actions of glucagon.
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