The Regulation of Gluconeogenesis in Isolated Rat Liver Cells by Glucagon, Insulin, Dibutyryl Cyclic Adenosine Monophosphate, and Fatty Acids

作者：Margaret E. Mayo Johnson, Naomi Mamota Das, Fred R. Butcher, John N. Fain · 发表于：Journal of Biological Chemistry · 年份：1972 · DOI：10.1016/s0021-9258(19)45235-6 · 被引用次数：180 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolism, Diabetes, and Cancer、Diet, Metabolism, and Disease

Abstract Suspensions of rat liver cells from starved rats converted three carbon precursors to glucose and responded to hormones such as glucagon and insulin. Cells were isolated by perfusion of rat livers with calcium-free Hanks' solution containing 0.01 g% of collagenase and 0.08 g% of hyaluronidase in the presence of 4% defatted albumin. Cells from 18- to 24-hour starved rats synthesized glucose de novo from l-alanine at rates comparable to those observed in the perfused liver. Glucagon increased cyclic adenosine 3',5'-monophosphate accumulation in liver cells with the maximal effect being observed some 2 min after its addition. In cells from fed rats there was an immediate increase due to glucagon of glucose release which could be accounted for by glycogenolysis. In cells from starved rats there was almost no glycogen (0.5% for starved rats as compared to 7.5% for fed rats), and there was a 20-min lag period before glucose output was increased by glucagon. Glucagon stimulated gluconeogenesis in the presence of alanine, lactate, or pyruvate whereas added fatty acids inhibited gluconeogenesis from alanine and stimulated that from lactate or pyruvate. Insulin increased glycogen deposition in cells from starved rats, and this accounted for the decrease in glucose output seen with insulin. Dibutyryl cyclic AMP also stimulated gluconeogenesis in isolated liver cells. The effects of insulin and glucagon on liver cells were abolished by short term treatment of cell suspensions wi...