Rate Of Hepatic Glycogenolysis Research Articles

The cytosolic concentration of phosphate determines the maximal rate of glycogenolysis in perfused rat liver

Glycogenolysis was studied in glycogen-rich perfused livers in which glycogen phosphorylase was fully converted into the a form by exposure of the livers to dibutyryl cyclic AMP. We monitored intracellular Pi by 31P n.m.r. Perfusion with Pi-free medium during 30 min caused a progressive decrease of the Pi signal to 50% of its initial value. In contrast, exposure of the livers to KCN and/or 2,4-dinitrophenol resulted in a rapid doubling of the Pi signal. Alterations in the intracellular Pi coincided with proportional changes in the rate of hepatic glycogenolysis (measured as the output of glucose plus lactate). The results indicate that the rate of glycogenolysis catalysed by phosphorylase a depends linearly on the hepatic Pi concentration. Hence the Km of phosphorylase a for its substrate Pi must be considerably higher than the concentrations that occur in the cytosol, even during hypoxia.

Human splanchnic metabolism during diabetic ketoacidosis

Splanchnic exchange rates of glucose, acetoacetate, β-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80–52.79) μmole/liter and total ketone-body concentration was 10.38 (6.04–15.81) mmole/liter. Net splanchnic glucose release was 0.77 (0.09–2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and α-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09–0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05–0.92) mmole/min and β-hydroxybutyrate release was 0.35 (−0.16 to 0.84) mmole/min. Total ketone-body release was 0.85 (0.37–1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenolysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.

Mechanism of epinephrine-hyperglycemia.

THE hyperglycemia and glycosuria produced by epinephrine described half a century ago as “adrenalin diabetes”—has been generally attributed to an increase in the rate of hepatic glycogenolysis. This concept is based on considerable, and apparently unequivocal, experimental evidence. It is well known, for instance, that in hepatectomized animals epinephrine does not produce hyperglycemia, and that in the perfused liver and in liver slices in vitro glucose output in increased by epinephrine. In a recent paper (Somogyi, 1950) we called attention to another, well defined phase of epinephrine action, namely inhibition of glucose assimilation,1 as a factor that contributes to epinephrine hyperglycemia. In that paper we confirmed the earlier findings of Wilenko (1913), Wiechman (1927), and Cori et al. (1928 and 1935), to the effect that epinephrine greatly depresses the rate of peripheral glucose assimilation. We expressed the view that this is a factor which potently enhances hyperglycemia.

A hyperglycemic factor extracted from the pancreas.

THE metabolic processes of the body are governed by compensating checks and balances which are frequently interdependent, some accelerating, some inhibiting specific processes. Among the most extensively studied of these activities is that of the factors, affecting carbohydrate metabolism. Insulin has, of course, been long known to be of prime importance to this process, but investigations have suggested that another substance obtained from the pancreas may also play a role in sugar metabolism. This substance has been found to produce hyperglycemia and increase the rate of hepatic glycogenolysis. There is at present no direct proof that the pancreatic hyperglycemic factor is functional under physiologic conditions. Results of cross-circulation experiments by Weinstein, Smith and Foa (1) have suggested that this may be true, but further observations are deemed necessary. Certain other evidence, both clinical and experimental, strongly supports this possibility and shall be briefly discussed at this time.

Changes in Blood Ketone Acids During Artificial Fever

SummaryArtificial hyperthermia in man increases ketosis. This, according to available evidence, is due to an increased rate of ketogenesis in the liver. Our observations on human subjects are in accord with the findings of previous investigators, who demonstrated on perfused liver, on liver slices and on living animals, that an inverse relationship exists between the glycogen content of the liver and the rate of ketone formation. The data presented indicate, moreover, that an increased rate of hepatic glycogenolysis per se suffices to increase ketosis, without any appreciable diminution of the glycogen reserves of the liver. An increased ketonemia in artificial fever can be entirely forestalled by the continuous injection of glucose so as to ensure the maintenance of blood sugar at hyperglycemic levels, a condition which enhances glycogen deposition in the liver and at the same time prevents an increase in the rate of glycogenolysis.