Changes In Glycogen Metabolism Research Articles

Glucose metabolism in amyotrophic lateral sclerosis: it is bitter-sweet.

Glucose metabolism in amyotrophic lateral sclerosis: it is bitter-sweet.

Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Chronic hepatitises of various etiologies are widespread liver diseases in humans. Their final stage, liver cirrhosis (LC), is considered to be one of the main causes of hepatocellular carcinoma (HCC). About 80–90% of all HCC cases develop in LC patients, which suggests that cirrhotic conditions play a crucial role in the process of hepatocarcinogenesis. Carbohydrate metabolism in LC undergoes profound disturbances characterized by altered glycogen metabolism. Unfortunately, data on the glycogen content in LC are few and contradictory. In this study, the material was obtained from liver biopsies of patients with LC of viral and alcohol etiology and from the liver tissue of rats with CCl4-induced LC. The activity of glycogen phosphorylase (GP), glycogen synthase (GS), and glucose-6-phosphatase (G6Pase) was investigated in human and rat liver tissue by biochemical methods. Total glycogen and its labile and stable fractions were measured in isolated individual hepatocytes, using the cytofluorometry technique of PAS reaction in situ. The development of LC in human and rat liver was accompanied by an increase in fibrous tissue (20- and 8.8-fold), an increase in the dry mass of hepatocytes (by 25.6% and 23.7%), and a decrease in the number of hepatocytes (by 50% and 28%), respectively. The rearrangement of the liver parenchyma was combined with changes in glycogen metabolism. The present study showed a significant increase in the glycogen content in the hepatocytes of the human and the rat cirrhotic liver, by 255% and 210%, respectively. An increased glycogen content in cells of the cirrhotic liver can be explained by a decrease in glycogenolysis due to a decreased activity of G6Pase and GP.

Abstract LB-296: Breast cancer metabolism in association with diabetes

Abstract Diabetes and cancer are diseases that have a tremendous impact on health worldwide. Epidemiologic evidence suggests that people with diabetes are at an increased risk of various cancers including liver, pancreas and breast cancer. In line with this, we are finding that breast cancer patients who have diabetes (both type I and II) have decreased breast cancer-specific survival, indicating that diabetes may affect tumor biology and increase disease aggressiveness. To further investigate how diabetes promotes the progression of breast cancer, we performed global metabolic profiling and gene expression analysis of matched tumors from 18 diabetes and 18 non-diabetes breast cancer patients. Patient characteristics in each group included 12 estrogen receptor-positive (ER+) and 6 ER-negative tumors from 14 African American and 4 European American patients. We also performed immunohistochemistry of key disease-associated marker proteins in tumors of these patients. Results from the metabolomic analysis showed a significant accumulation of glycogen metabolic intermediates in breast tumors of diabetes patients, indicating changes in glycogen metabolism in tumor biology. Gene expression analysis showed differential expression of more numerous transcripts in the diabetic vs non-diabetic tumors. Interestingly, the top gene on this list was PPP1R3C, a gene involved in regulation of glycogen metabolism. We validated the higher expression of PPP1R3C in diabetic breast tumors by qRT-PCR and are currently performing an immunohistochemical evaluation of FFPE tumors. Other immunohistochemical staining of tumors from diabetic and non-diabetic patients showed significantly higher stromal expression of indolamine-2,3-dioxgenase (IDO) in breast tumors associated with diabetes, which indicates an immunosuppressive tumor microenvironment. To further corroborate our patient studies in cell culture systems, we began to use cytokine arrays in order to examine media of breast cancer cells treated with high glucose, which potentially mimics diabetes condition in cell culture. As a preliminary observation, we noticed a decrease in the level of certain cytokines in ER+ breast cancer cells (MCF7 and T47D). Notably, these cytokines remained unaltered in the conditioned media of non-neoplastic cells (MCF10A, MCF12A) grown under high glucose. Thus, under high glucose condition, ER+ breast cancer cells may secret a different cytokine repertoire, which would prevent recruiting immune cells into the tumor microenvironment and thereby may create an immunosuppressive tumor microenvironment. In conclusion, our current data indicate that diabetes may promote breast cancer progression by altering glycogen metabolism and by creating an immunosuppressive tumor microenvironment, which we currently further investigate. Citation Format: Gatikrushna Panigrahi, Tiffany H. Dorsey, Wei Tang, Stefan Ambs. Breast cancer metabolism in association with diabetes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-296.

Mitochondria, glycogen, and lipid droplets in skeletal muscle during testosterone treatment and strength training: a randomized, double-blinded, placebo-controlled trial.

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double-blinded, placebo-controlled study, we investigated the effects of six-month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin-stimulated Rd) and body composition were assessed by euglycemic-hyperinsulinemic clamp and dual X-ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p<0.05), whereas percent body fat decreased (p<0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ=-0.43; p=0.003). Δ-mitochondrial fraction correlated positively with Δ-total testosterone (ρ=0.70; p=0.02), and Δ-glycogen fraction correlated inversely with Δ-LBM (ρ=-0.83; p=0.002) during six-month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small-scale study, the beneficial effects of six-month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six-month ST or combined three-month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons.

Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE‐NPYD βH) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti‐hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE‐NPYD βH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild‐type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE‐NPYD βH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE‐NPYD βH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

13C MRS Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

Introduction: Glycogen is the primary intracellular storage form of carbohydrates. In contrast to most tissues where stored glycogen can only supply the local tissue with energy, hepatic glycogen is mobilized and released into the blood to maintain appropriate circulating glucose levels, and is delivered to other tissues as glucose in response to energetic demands. Insulin and glucagon, two current targets of high interest in the pharmaceutical industry, are well known glucose-regulating hormones whose primary effect in liver is to modulate glycogen synthesis and breakdown. The purpose of these studies was to develop methods to measure glycogen metabolism in real time non-invasively both in isolated mouse livers, and in non-human primates (NHPs) using 13C MRS. Methods: Livers were harvested from C57/Bl6 mice and perfused with [1-13C] Glucose. To demonstrate the ability to measure acute changes in glycogen metabolism ex-vivo, fructose, glucagon, and insulin were administered to the liver ex-vivo. The C1 resonance of glycogen was measured in real time with 13C MRS using an 11.7T (500 MHz) NMR spectrometer. To demonstrate the translatability of this approach, NHPs (male rhesus monkeys) were studied in a 7 T Philips MRI using a partial volume 1H/13C imaging coil. NPHs were subjected to a variable IV infusion of [1-13C] glucose (to maintain blood glucose at 3-4x basal), along with a constant 1 mg/kg/min infusion of fructose. The C1 resonance of glycogen was again measured in real time with 13C MRS. To demonstrate the ability to measure changes in glycogen metabolism in vivo, animals received a glucagon infusion (1 μg/kg bolus followed by 40 ng/kg/min constant infusion) half way through the study on the second study session. Results: In both perfused mouse livers and in NHPs, hepatic 13C-glycogen synthesis (i.e. monotonic increases in the 13C-glycogen NMR signal) was readily detected. In both paradigms, addition of glucagon resulted in cessation of glycogen synthesis and induction of glycogen breakdown. In the perfused liver, inclusion of insulin was able to dose-dependently block the effect of glucagon. Conclusion: Hepatic glycogen synthesis, as well as acute hormonally-induced changes thereof, can be measured using 13C MRS at high magnetic fields both ex-vivo

Glycogen Synthesis in Glycogenin 1-Deficient Patients: A Role for Glycogenin 2 in Muscle.

Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup. A likely candidate is glycogenin 2, an isoform expressed in the liver and heart but not in healthy skeletal muscle. We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD type XV. Two patients with mutations in the GYG1 gene were investigated for histopathology, ultrastructure, and expression of proteins involved in glycogen synthesis and metabolism. Apart from occurrence of polyglucosan (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients with GSD type XV. We found that glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas the opposite was the case in healthy controls. Electron microscopy revealed that glycogen was present between and not inside myofibrils in type II fibers, compromising the ultrastructure of these fibers, and only type I fibers contained PG bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism. To our knowledge, this is the first report demonstrating expression of glycogenin 2 in glycogenin 1-deficient patients, suggesting that glycogenin 2 rescues the formation of glycogen in patients with glycogenin 1 deficiency.

Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States.

Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions.

α-Actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle

Approximately one billion people worldwide are homozygous for a stop codon polymorphism in the ACTN3 gene (R577X) which results in complete deficiency of the fast fibre muscle protein alpha-actinin-3. ACTN3 genotype is associated with human athletic performance and alpha-actinin-3 deficient mice [Actn3 knockout (KO) mice] have a shift in the properties of fast muscle fibres towards slower fibre properties, with increased activity of multiple enzymes in the aerobic metabolic pathway and slower contractile properties. alpha-Actinins have been shown to interact with a number of muscle proteins including the key metabolic regulator glycogen phosphorylase (GPh). In this study, we demonstrated a link between alpha-actinin-3 and glycogen metabolism which may underlie the metabolic changes seen in the KO mouse. Actn3 KO mice have higher muscle glycogen content and a 50% reduction in the activity of GPh. The reduction in enzyme activity is accompanied by altered post-translational modification of GPh, suggesting that alpha-actinin-3 regulates GPh activity by altering its level of phosphorylation. We propose that the changes in glycogen metabolism underlie the downstream metabolic consequences of alpha-actinin-3 deficiency. Finally, as GPh has been shown to regulate calcium handling, we examined calcium handling in KO mouse primary mouse myoblasts and find changes that may explain the slower contractile properties previously observed in these mice. We propose that the alteration in GPh activity in the absence of alpha-actinin-3 is a fundamental mechanistic link in the association between ACTN3 genotype and human performance.

The Comparative Pathology of the Glycosidase Inhibitors Swainsonine, Castanospermine, and Calystegines A3, B2, and C1 in Mice

To study various polyhydroxy-alkaloid glycosidase inhibitors, 16 groups of 3 mice were dosed using osmotic minipumps with swainsonine (0, 0.1, 1, and 10 mg/kg/day), castanospermine, and calystegines A(3), B(2), and C(1) (1, 10, and 100 mg/kg/day). After 28 days, the mice were euthanized, necropsied, and examined using light and electron microscopy. The high-dose swainsonine-treated mice developed neurologic disease with neuro-visceral vacuolation typical of locoweed poisoning. Castanospermine- and calystegines-treated mice were clinically normal; however, high-dose castanospermine-treated mice had thyroid, renal, hepatic, and skeletal myocyte vacuolation. Histochemically, swainsonine- and castanospermine-induced vacuoles contained mannose-rich oligosaccharides. High-dose calystegine A(3)-treated mice had increased numbers of granulated cells in the hepatic sinusoids. Electron microscopy, lectin histochemistry, and immunohistochemistry suggest these are pit cells (specialized NK cells). Histochemically, the granules contain glycoproteins or oligosaccharides with abundant terminal N-acetylglucosamine residues. Other calystegine-treated mice were histologically normal. These findings indicate that swainsonine produced lesions similar to locoweed, castanospermine caused vacuolar changes with minor changes in glycogen metabolism, and only calystegine A(3) produced minimal hepatic changes. These also suggest that in mice calystegines and castanospermine are less toxic than swainsonine, and as rodents are relatively resistant to disease, they are poor models to study such induced storage diseases.

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

Regulation of glycogen metabolism in hepatocytes through adenosine receptors. Role of Ca 2+ and cAMP

The objective of this work is to identify the adenosine receptor subtype and the triggered events involved in the regulation of hepatic glycogen metabolism. Glycogenolysis, gluconeogenesis, cAMP, and cytosolic Ca 2+ ([Ca 2+] cyt) were measured in isolated hepatocytes challenged with adenosine A 1, A 2A, and A 3 receptor-selective agonists. Stimulation of adenosine receptor subtypes with selective agonists in Ca 2+ media produced a dose-dependent increase in [Ca 2+] cyt with A 1>A 2A=A 3, cAMP with A 2A, glycogenolysis with A 1>A 2A>A 3, and gluconeogenesis with A 2A>A 1>A 3, in addition, a decrease in cAMP was observed with A 1=A 3. Comparatively, in Ca 2+-free media or with a cell membrane-permeant Ca 2+ chelator, activation of these adenosine receptors with the same selective agonists produced a smaller and transient rise in [Ca 2+] cyt with A 1=A 3>A 2, no rise in glycogenolysis and gluconeogenesis with A 3>A 1, but a full rise with A 2A. Thus, in isolated rat hepatocytes activation of the adenosine A 1 receptor triggered Ca 2+-mediated glycogenolysis, activation of the adenosine A 2A receptor stimulated cAMP-mediated gluconeogenesis, and activation of the adenosine A 3 receptor increased [Ca 2+] cyt and decreased cAMP with minor changes in glycogen metabolism.

Glycogen levels and glycogen catabolism in livers from arthritic rats.

Hepatic glycogen catabolism and glycogen levels in rats with chronic arthritis were investigated. At 9:00 a.m., the hepatic glycogen contents of ad libitum fed arthritic and normal rats were 225.5+/-17.7 and 332.1+/-28.6 micromol glucosyl units x (g liver)(-1), respectively. Food intake of arthritic and normal rats was equal to 100.1+/-6.7 and 105.0+/-3.1 mg x (g body w)(-1) x (per 24 h)(-1), respectively. In isolated perfused livers from normal and arthritic rats the rates of glucose, lactate and pyruvate release were the same when substrate- and hormone-free perfusion was performed. During an infusion period of 20 min glucagon caused an increment in glucose release of 35.3+/-4.7 micromol x (g liver)(-1) in livers from arthritic rats; in the normal condition the corresponding increment was 69.6+/-5.7 micromol x (g liver)(-1). Lactate and pyruvate productions (indicators of glycolysis) were diminished by glucagon in livers from normal rats; in the arthritic condition an initial stimulation was found, followed by a slow decay, which did not result in significant inhibition at the end of the glucagon infusion period (20 min). The actions of cAMP and dibutyryl-cAMP were similar to those of glucagon. It was concluded that livers from arthritic rats show an impaired capacity of releasing glucose under the stimulus of glucagon. This can be partly due to the lower glycogen levels and partly to a smaller capacity of inhibiting glycolysis. Reduction in glycogen levels was not associated with reduction in food intake or failure in the energetic state of the hepatic cells. These changes in glycogen metabolism may be related to reduced gluconeogenic capacity of the livers and/or to production of inflammatory mediators observed in the arthritis disease.

Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction.

Exercise has numerous growth and metabolic effects in skeletal muscle, including changes in glycogen metabolism, glucose and amino acid uptake, protein synthesis and gene transcription. However, the mechanism(s) by which exercise regulates intracellular signal transduction to the transcriptional machinery in the nucleus, thus modulating gene expression, is largely unknown. This review will provide insight on potential intracellular signalling mechanisms by which muscle contraction/exercise leads to changes in gene expression. Mitogen-activated protein kinase (MAPK) cascades are associated with increased transcriptional activity. The MAPK family members can be separated into distinct parallel pathways including the extracellular signal-regulated kinase (ERK) 1/2, the stress-activated protein kinase cascades (SAPK1/JNK and SAPK2/p38) and the extracellular signal-regulated kinase 5 (ERK5). Acute exercise elicits signal transduction via MAPK cascades in direct response to muscle contraction. Thus, MAPK pathways appear to be potential physiological mechanisms involved in the exercise-induced regulation of gene expression in skeletal muscle.

Patients with chronic glucocorticoid treatment develop changes in muscle glycogen metabolism

High dose glucocorticoid may induce a significant myopathy with loss of thick myofilament from muscle, particularly if administered in conjunction with depolarizing drugs. Remarkably, the effect of chronic low dose glucocorticoid in muscle is vastly different, although it may induce changes in muscle glycogen metabolism as evidenced in animal experimental trials. However, there is no clear confirmation that these changes could develop similarly in patients. We evaluate clinical, functional, histological and metabolic muscle changes during chronic low-dose glucocorticoid treatment in 11 asthmatic patients. Remarkably, these patients did not develop clinical symptoms of myopathy nor significant muscle weakness or morphological changes in muscle histology. However, glycogen concentration and the activity of the main regulatory enzymes of glycogen metabolism, aldolase and creatine kinase were modified in comparison with controls. An increase in the synthesis and muscle cell deposition of glycogen and a decrease in the muscle glycogen degradation process have been suggested. These changes were not related with malnutrition. There was not correlation between histological and biochemical changes. We conclude that chronic treatment with glucocorticoid causes clear changes in glycogen metabolism in the skeletal muscle, resulting in glycogen muscle storage. The significance of these biochemical changes is unknown, but it can be well an associated phenomenon with glucocorticoid treatment.

Effects of the administration of angiotensin II on cardiac glycogen metabolism in the rat

Changes in glycogen metabolism after an intravenous injection of angiotensin II were investigated in the left and right ventricles of the rat heart, as a function of location within the ventricular wall. Hearts were cut into 100-microns thin section, all of which were analysed for glycogen content, glucose incorporation into glycogen and 2-deoxyglucose uptake and phosphorylation after the intravenous injection of 14C-labelled sugar. In control hearts, glycogen levels were uniform across the wall in both ventricles, while the rate of sugar uptake and phosphorylation, and that of glucose incorporation into glycogen, were significantly higher in the subendocardial myocardium of the left ventricular wall. After angiotensin II administration, heart glycogen levels decreased slightly in the left, but not in the right ventricle, while 2-deoxyglucose uptake and phosphorylation, and glucose incorporation into glycogen, increased 2,5- and 5-fold, respectively. With regard to the distribution across the wall of the left ventricle after angiotensin administration, glycogen levels and glucose incorporation into glycogen were uniformly distributed, whereas sugar phosphorylation was still higher in the subendocardium.

Toxicity of the pyrethroid insecticide fenvalerate to a fresh water fish, Tilapia mossambica (Peters): Changes in glycogen metabolism of muscle

Toxic effects of a pyrethroid insecticide, fenvalerate, on fish muscle glycogen metabolism were investigated. Estimations were made after 10 and 20 days of exposure, and altered muscle glycogen metabolism was observed. The changes included a significant ( P < 0.001) decrease in the levels of glycogen, pyruvate, maleate dehydrogenase (MDH), succinate dehydrogenase (SDH), and phosphorylase a, b, and ab activities, while elevated levels of lactic acid, aldolase, and lactate dehydrogenase (LDH) activity were observed under fenvalerate intoxication. There was a decrease in opercular movement and oxygen consumption with an increase in concentration of fenvalerate.

Chick myotubes in culture express high-affinity receptors for calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide that is expressed by many neurons of the vertebrate nervous system, including motoneurons of many species. It has been detected immunohistochemically in both cell bodies and motor terminals of motoneurons, suggesting that it may play a role at the neuromuscular junction. In support of this idea, CGRP has been shown to produce a variety of effects on cultured myotubes and muscle explants, including elevation of cAMP levels, increase in cell-surface acetylcholine receptor (AChR) numbers, increase in AChR α-subunit mRNA transcript levels, alterations in contractile responses, alterations in the physiological properties of AChRs, and inhibition of insulin-induced changes in glycogen metabolism. CGRP binding sites have been detected in many tissues, but have not yet been demonstrated directly on muscle cells. Here we report that chick myotubes in culture express high-affinity binding sites for CGRP ( K d approximately 2–4×10 −10 M). In view of the known biological effects of CGRP on myotubes, we believe that these binding sites represent CGRP receptors. They are uniformly distributed over the surface of myotubes, and we have found no evidence of clustering in culture, in contrast to AChRs. We have found no evidence for more than one class of receptors.

Changes of glycogen metabolism in phosphorylcreatine-depleted muscles taken from rats fed with beta-guanidine propionate

Changes in glycogen metabolism were explored in fast and slow muscles taken from rats fed with a diet containing 1% beta-guanidine propionate (GPA), a synthetic analog that inhibits the entry of creatine into muscle cells competitively and causes phosphorylcreatine depletion. Feeding with the GPA-containing diet increased glycogen levels in the two types of muscles to a different extent and with different temporal patterns; it did not change significantly the rate of glycogen turnover both at rest and during exercise; it did not affect the net degradation of glycogen during exercise. Diet could affect the activity of several enzymes of sugar metabolism. These latter changes too were different in fast-twitch and in slow-twitch muscles.

Acclimation to sublethal acidic and alkaline media of Tilapia mossambica (Peters): changes in glycogen metabolism of red muscle.

Freshwater bodies at several parts of the globe are presently undergoing progressive acidification due to acid precipitation and acid mine drainage. Significant changes under altered pH stress includes reduced primary production of algal biomass, benthic communities and rapid decline in fish populations. Studies dealing with the physiological responses of fish to acidic and alkaline water pollution are very limited. Hence, the studies dealing with the biological impact of acidity and alkalinity on the physiology and biochemistry of freshwater fish has been undertaken.