In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose.

Abstract

A B S T R A C T Studies were conducted to determine whether the direction ofhepatic 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 either glycogen synthesis or lipogenesis. The best precursor for glycogen formation was fructose, whereas lactate (pyruvate) was most efficient in lipogenesis. In both cases 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 portal blood during feeding) facilitates the uptake of glucose by liver it seems

Hepatocyte insulin binding and action in rats with sommatomammotrophic tumours

“…There was no accumulation of glycogen in these cells during incubation in agreement with other reports studying hepatocytes incubated with glucose [23][24][25].…”

Effect of Dietary Soybean Phospholipid and Fats Differing in the Degree of Unsaturation on Fatty Acid Synthesis and Oxidation in Rat Liver.

“…Malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase represents a mechanism by which mitochondrial oxidation of long-chain fatty acids is regulated (29). As malonyl-CoA is the enzyme product of acetyl-CoA carboxylase, its concentration in the liver proportionally decreases as the rate of fatty acid synthesis decreases (30). Thus, depression by soybean phospholipid of hepatic fatty acid synthesis should decrease the malonyl-CoA concentration in the liver and in turn enhance the rate of fatty acid oxidation even when the activities of the If the depression of fatty acid synthesis is a factor primarily responsible for the lipid-lowering effect of soybean phospholipid(1-9), the lipid-lowering effect of the phospholipid should be diminished under the condition in which hepatic fatty acid synthesis is hampered.Dietary polyunsaturated fatty acids compared to saturated fatty acids has been reported to be more competent in reducing the rate of fatty acid synthesis in the liver (12,19 It has been well demonstrated that dietary phospholipid decreases serum cholesterol concentration in the rat (1-3).…”

Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase

“…Accordingly, precursors of F1P, such as fructose or sorbitol (16), are likely to be important for glucose clearance by liver after a meal. Indeed, supply of fructose together with glucose was shown to increase glycogen synthesis by liver in the rat and dog (32,33). Although fructose can be efficient to relieve hyperglycemia in diabetes, the use of fructose as a substituent for glucose for diabetes patients has raised the controversy (34,35).…”