Changes In Glycogen Metabolism Research Articles

Effect of denervation on glycogen metabolism in fast and slow muscle of rat.

The postdenervation changes in glycogen metabolism were explored in fast (extensor digitorum longus, EDL), and slow (soleus, S) muscle of rat. During the first 12-14 hours after denervation, glycogen accumulates to a similar content in the two muscles, an effect reproduced by paralysis. Increase in the molecular weight of glycogen and decrease in the turnover rate of similar degree occur. During the ensuing 12-24 hours the glycogen concentration decreases in EDL (but not in S). This decrease is influenced by factors such as muscle type, longer or shorter nerve stump, age, and previous training of the animal. In both EDL and S, the rate of glucose incorporation into glycogen and the glycogen synthase [l/(l + D)] activity were depressed by denervation. The cAMP concentration increased 36 hours after denervation. This may have consequences on the muscle sensitivity to hormones. In fact, at this time, insulin did not increase glycogen synthase I activity or the glycogen content (with the exception of glycogen in S) and the effects of epinephrine on glycogen metabolism became more significant.

Transmural gradient of glycogen metabolism in the normal rat left ventricle.

The changes of glycogen metabolism with the location of tissue within the ventricle wall have been explored in the rat myocardium. The hearts were cut in 100 microns thick serial sections and all sections were analyzed for their content in glycogen, glucose-6-phosphate, UDPG and glycogen enzymes and for glucose incorporation into glycogen and for the 2-deoxyglucose uptake after the intravenous injection of the 14C-labelled sugars. The rate of glycogen turnover was significantly higher in the subendocardial myocardium (P less than 0.01) and the levels of glucose-6-phosphate and the total (i.e. a + b) activity of glycogen phosphorylase were significantly higher in the subepicardial tissue (P less than 0.01 in both instances). No significant transmural gradient of UDPG was found and transmural changes of total (i.e. I + D) synthase activity were barely significant. These changes in glycogen metabolism may be related to regional differences in the cardiac work load and to a differentiation of the subendocardial and subepicardial heart fibers.

Glycogen metabolism and the function of fast and slow muscles of the rat.

Changes in glycogen metabolism with function have been explored in a fast (the extensor digitorum longus, EDL) and in a slow (the soleus, S) muscle of rat. The rate of glucose incorporation is not related to the glycogen levels. In the S glycogen levels are lower and glucose incorporation is higher than in EDL and differences almost disappear after denervation and increase with exercise. In the S, synthetic activities may be higher and glycogenolytic activities are lower than in the EDL. The levels are given of many substrates and cofactors which can affect glycogen enzymes "in vivo". On the whole, the data indicate that the rate of glycogen turnover can change dramatically with muscle function even at very light work load and may be higher in the so called oxidative than in the glycolytic muscles.

Hepatic glycogen metabolism and its regulation by hormones in pouch young of the tammar wallaby, Macropus eugenii (Desmarest)

Glycogen metabolism was studied in isolated parenchymal cells from livers of 180- to 220-day-old pouch young of the tammar wallaby, Macropus eugenii. The integrity of the hepatocytes was tested by a number of criteria to ensure their metabolic viability. The concentration of hepatic glycogen was about 50-fold lower in 24-hr-fasted animals than in fed animals. Isolated hepatocytes from fasted animals produced very little glucose during incubation while cells from fed animals produced glucose at a rate which was positively correlated with the concentration of glycogen in the cells. Loss of glycogen from the cells was also measured in the presence of a number of gluconeogenic substrates. Glycogen was conserved in the presence of fructose, but alanine, glycerol, propionate, lactate, or pyruvate had no consistent effect on glycogen levels. Glucagon (10 −9 M, 10 −8 M), epinephrine (10 −5 M), and dibutyryl cyclic AMP (10 −5 M, 10 −3 M) had no effect on glucose production by cells from fasted animals, but increased glucose production by cells from fed animals. Insulin (10 −6 M) reduced glucose production only in cells with high (greater than 1 μmol glucosyl units/10 6 cells) glycogen concentrations. Insulin also antagonized the effects of glucagon and epinephrine on glucose production by cells from fed pouch young. The effects of the hormones are probably attributable to changes in glycogen metabolism rather than gluconeogenesis.

Ultrastructural changes in beta-cells of pancreatic islets in alpha-amanitin-poisoned mice.

In mice poisoned by alpha-amanitin nuclear changes typical of this toxin were observed in beta-cells of pancreatic islets. The lesions became progressively more severe and at 48 h after toxin injection some cells were necrotic. The damage to these cells could have implications in the changes in glycogen metabolism which occur after alpha-aminitin poisoning.

Glycogen metabolism in adult rat liver parenchymal cell primary cultures

Parenchymal cells were isolated from adult rat liver with an enzyme perfusion technique. The single-cell suspension, representing 40-50% of the liver's hepatocytes was suspended in medium and maintained in primary culture for up to four days. The cells were found to carry out glycogen synthesis for the first eight hours in culture after which time the accumulated glycogen was gradually degraded. The ability of the liver cell cultures to accumulate glycogen was found to be dependent upon the metabolic state of the animal prior to cell isolation. Cells prepared during the feeding period from animals on the 8+16 feeding schedule had markedly different capacities for glycogen accumulation. Changes in glycogen metabolism were found to be due, in part, to changes in the fraction of cells involved in metabolism at any given time. High concentrations of glucose stimulated the cells to deposit glycogen but the response was reduced the longer the cells were in culture over a 3-day period. This loss of glycogen synthesizing capacity appears to be due to a decrease in glycogen synthetase activity. The activities of pyruvate kinase, hexokinase and aldolase also decrease during the culture period.

The Interdependence of Mitochondrial Maturation and Glycogen Metabolism in Perinatal Rat Liver

The processes involved in differentiation and morphogenesis of a multicellular organism encompass many different aspects of molecular and cellular biology. In recent years the tendency has been to explain developmental changes mainly in terms of transcriptional and translational control of protein synthesis (Davidson & Britten, 1971 ; Rutter et al., 1973; Paul, 1974). Changes in enzyme activities during development and differentiation have been studied for some time (for reviews, see Herrmann & Tootle, 1964; Moog, 1965; Knox, 1972); in particular, the changing patterns of enzyme activities and enzyme induction in hepatocytes of the perinatal rat have been investigated in considerable detail (for reviews, see Dawkins, 1966; Greengard, 1971). It has been observed that in rat liver increases in enzyme activities occur during three well-defined developmental periods, the latefoetal, the neonatal and the late-suckling clusters (Greengard, 1971). The most dramatic changes occur, as expected, during the late-foetal and immediate-neonatal period and they appear to involve transcriptional as well as chain-termination controls of translation on the ribosome (Yeung & Oliver, 1968; Chuah & Oliver, 1971). The influences that membranous organelles may exert either on the expression of the genome or on the effective expression of gene products have been relatively little explored. Yet it should be emphasized that the qualitative changes as well as the distribution of membranous organelles within eukaryote cells are not only an end result of differentiation, but these organelles have the potential to prevent, enhance or modulate the expression of some genes and gene products (Berendes et al., 1975; Duck-Chong & Pollak, 1973). The enzyme activities of the differentiating hepatocyte may be influenced by changes in the permeability barriers of the membranous organelles or, in the case of membrane-bound enzymes, changes in membrane composition may bring about allotropic changes in enzyme activities (Racker, 1970). In this review I want to address myself especially to the part played by mitochondrial maturation and to the effect which the interaction of these matured mitochondria with other cellular compartments has on the differentiation of hepatocytes. In addition, I shall attempt to provide an overview of the interacting mechanisms that are currently considered to trigger-off and control the changes in glycogen metabolism occurring at parturition in rat liver.

Changes in glycogen phosphorylase activity and glycogen levels of mouse cerebral cortex during convulsions induced by homocysteine.

Abstract—Glycogen phosphorylase activity and glycogen levels were investigated in the cerebral cortex of mice of two different strains under the influence of homocysteine. Control levels of glycogen and total phosphorylase activity (i. e. activity in the presence of 1 mM‐AMP) were higher in the inbred strain A, whereas a higher proportion of phosphorylase in its active form (activity without 5′‐AMP) was obtained in the ICR strain (probably due to slower fixation of brain in this strain). Changes occurring after the administration of homocysteine were similar in both strains. With the onset of first clonic seizures a marked increase of phosphorylase a occurred (increase 99 per cent in strain A and 46.5 per cent in ICR, respectively). During the latter phase of tonic seizures active phosphorylase a did not significantly differ from control values. Five minutes after the end of a tonic seizure, i. e. when partial recovery could already be observed, a marked decrease of active phosphorylase a in comparison with control values, was evident (decrease against control values of 45.5 per cent in strain A and 30.5 per cent in ICR, respectively). The total phosphorylase activity was not affected in strain A, whereas a slight increase during clonic seizures was seen in the ICR strain. In accordance with the enhanced activation of phosphorylase at the onset of clonic seizures, a marked decrease in glycogen levels (35‐50 per cent) was observed in both strains of mice. This decrease persisted even during the 5 min recovery period. When seizures were prevented by Na phenobarbital or glycine, the activation of phosphorylase was either completely prevented (by a non‐anaesthetic dose of phenobarbital) or reduced (by glycine). The present results have demonstrated that changes in glycogen metabolism occurring during homocysteine seizures differ distinctly from those previously found during seizures induced by methionine sulphoximine, a substance structurally related to homocysteine.

Effects of metformin on glucose uptake by isolated diaphragm from normal and diabetic rats

The effects of the antidiabetic drug metformin (Nl, Nl-dimethylbiguanide) on glucose uptake by isolated rat diaphragm muscle have been studied. A therapeutic concentration of metformin (10 μg/ml) had no effect on glucose uptake by diaphragm muscle from normal rats incubated in the absence or presence of insulin (100 and 1000 μU/ml), but increased uptake by diaphragm muscle from alloxan-diabetic rats incubated in the presence of insulin (P < 0.05). Diaphragm muscle from normal rats incubated in a medium containing sodium butyrate (0.25 mg/ml) showed a reduction in glucose uptake similar to that seen in muscle from diabetic animals. Metformin (10 μg/ml) also increased glucose uptake by this preparation in the presence of insulin (P < 0.01). A higher concentration of metformin (100 μg/ml) caused a depression of glucose uptake by diaphragms from normal rats, and the necessity for studying therapeutic concentrations of the biguanide drugs is stressed. The relation of these findings to the antidiabetic effect of the drug in man is discussed. The mechanisms involved are discussed in terms of changes in glycogen metabolism.

Glycogen Metabolism following Ultraviolet Irradiation

Using mini pigs as experimental animals, histochemical and biochemical changes in glycogen metabolism following UV light irradiation were investigated. The most remarkable change observed in the first 4 hours post irradiation was a decrease in the glycogen concentration. This decrease might be due to the release of lysosomal α-glucosidase. After the first 4 hours there was a sharp increase in the percent of glycogen synthetase present in the I-form (peak at 10 hours) and in the rate of glycogen formation. This was followed by a peak of glycogen concentration at approximately 15 hours after irradiation.

Synthesis of liver glycogen in starved alloxan diabetic rats.

Alloxan diabetic rats are considered unable to synthesize liver glycogen because of a low activity of glycogen synthetase. The present report shows, however, that livers of alloxan diabetic rats have activities of the I-form of glycogen synthetase intermediate between those of starved normal or adrenalectomized rats, and can synthesize substantial amounts of liver glycogenafter refeeding of a chow diet or administration of hydrocortisone. Neither glycogenic procedure, increased the activity of glycogen synthetase in livers of starved alloxan diabetic rats. In contrast, both normal and adrenalectomized rats had increased activities of the I-form of glycogen synthetase three hours after refeeding. After twenty-four hours of access to food, normal and adrenalectomized rats had liver glycogen contents similar to those found in nonstarved rats, and a markedly decreased activity of synthetase I. Alloxan diabetic rats refed for twenty-four hours also had lowered activity of synthetase I, but the concentration of glycogen was not higher than that found after three hours of refeeding. These results show that livers of alloxan diabetic rats have sufficient glycogen synthetase activity to synthesize glycogen rapidly, but the ability to accumulate larger amounts of glycogen is limited by an alteration in the control of glycogen synthetase activity by the content of liver glycogen. Also, the effect of hydrocortisone on the activity of glycogen synthetase in normal or adrenalectomized rats is the result of insulin release; however, not all the changes in glycogen metabolism produced by adrenalectomy can be explained by insulin deficiency.

Biochemical changes in rat liver after acute beryllium poisoning

Rats were injected intravenously with 0.75 mg Be/kg and the effects upon liver metabolism were investigated within the first 24 hr. Poisoned animals showed an impaired loss of liver glycogen during fasting. Studies upon the incorporation of labelled glucose into liver glycogen, the ability of poisoned livers to resynthesize glycogen and determination of the concentration of glucose-6-phosphate failed, however, to establish a relationship between changes in glycogen metabolism in vivo and the highly specific inhibition of phosphoglucomutase by beryllium in vitro. Microsomal, lysosomal and mitochondrial enzyme systems were little affected. Therefore, no specific action of beryllium was found and though a very powerful necrogenic agent, beryllium differs markedly from other hepatotoxins.