Decrease In Liver Glycogen Content Research Articles

Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats.

The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 106 cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.

Effect of cadmium on glycogen content in muscle, liver, gill and kidney tissues of freshwater fish Channa punctatus (Bloch)

Aquatic environment gets polluted by heavy metals because of their environmental persistence and ability to bioaccumulate in aquatic organisms. Cadmium is a ubiquitous toxic heavy metal, biologically non-essential element, it is not biodegradable and has a very long biological half-life. The aim of the present study was to assess the glycogen content in muscle, liver, gill and kidney of Channa punctatus exposed to sublethal concentrations of cadmium chloride after 4, 7, 15 and 30 days of exposure. The results clearly showed significant decrease in the glycogen levels in the experimental fish C. punctatus. Decrease in muscle glycogen was found highly significant (P<0.001) after 30 days in both low concentration (36.823 mg/L) 6.12±0.41mg/g and in high concentration (73.646 mg/L) 4.04±0.32 mg/g in comparison to control. Decrease in liver glycogen content was found highly significant (P<0.001) after 30 days in high concentration 9.12±0.49 mg/g when compared with control. The decrease in gill glycogen content after 30 days exposure was found highly significant (P<0.001) 1.36±0.13 mg/g in low concentration and in high concentration 0.79±0.25 mg/g in comparison to control. Decrease in kidney glycogen content was found highly significant (P< 0.001) at 30 days in low concentration 3.92±0.05 mg/g and in high concentration 2.81±0.20 mg/g in comparison to control. The influence of toxicant cadmium chloride in selected tissues of fish was taken into account in evaluating fish response against stressor. Hence, we can use glycogen content as biomarker of cadmium stress in fish.

Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression.

Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder caused by a deficiency of glycogen-debranching enzyme (GDE), which results in profound liver metabolism impairment and muscle weakness. To date, no cure is available for GSDIII and current treatments are mostly based on diet. Here we describe the development of a mouse model of GSDIII, which faithfully recapitulates the main features of the human condition. We used this model to develop and test novel therapies based on adeno-associated virus (AAV) vector-mediated gene transfer. First, we showed that overexpression of the lysosomal enzyme alpha-acid glucosidase (GAA) with an AAV vector led to a decrease in liver glycogen content but failed to reverse the disease phenotype. Using dual overlapping AAV vectors expressing the GDE transgene in muscle, we showed functional rescue with no impact on glucose metabolism. Liverexpression of GDE, conversely, had a direct impact on blood glucose levels. These results provide proof of concept of correction of GSDIII with AAV vectors, and they indicate that restoration of the enzyme deficiency in muscle and liver is necessary to address both the metabolic and neuromuscular manifestations of the disease.

Detraining Leads to Weight Gain and a Decrease in Hepatic Glycogen after 8 Weeks of Training

Many studies have evaluated the effects of physical training on several metabolic parameters, but few studies have been conducted to evaluate the effects of detraining on these variables. Female mice were distributed into three experimental groups: sedentary controls (C-SED, not trained), trained controls (TR, trained for 10 weeks) and a detraining group (DT, animals detrained for 2 weeks after 8 weeks of training). The exercise protocol was performed by swimming applied for 60 min/day on 5 days/week. The DT group showed an increase of body weight in the 10th week when compared to the 8th week (after training cessation) and the TR group. The groups did not show differences in the plasma levels of corticosterone, glucose, total cholesterol or triglycerides. The DT group showed decreased glycogen content when compared to the TR group. No significant differences were found in the gene expression of glycogen synthase or glycogen phosphorylase or in hepatic glycogen content between CT and TR or DT group. We verified that after a training period of 8 weeks, the animals had an increase in body weight after two weeks of detraining. After two weeks of detraining, animals showed a decrease in liver glycogen content, without an altered fasting glucose concentration in their plasma.

Free radical scavenging and hepatoprotective activity of HD-03/ES in experimental models

Objective: Present study was aimed to evaluate the nonspecific hepatoprotective activity of HD-03/ES, a herbal combination, against experimental model of carbon tetrachloride (CCl4)-induced hepatic damage, and also free radical scavenging activity by using different in vitro antioxidant assay systems. Methods: The hepatoprotective activity of HD-03/ES was evaluated using an experimental model of CCl4-induced hepatic damage. The liver marker enzymes such as serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) were estimated apart from liver glycogen content and routine histopathological evaluation of liver samples. The free radical scavenging activity of HD-03/ES was evaluated by in vitro methods such as 2,2-Diphenyl-1-picrylhydrazyl (DPPH), reducing power (Fe3+-Fe2+) and oxygen radical absorbance capacity (ORAC) assays. Results: Administration of CCl4 to rats showed significant elevation of SGPT, SGOT and decrease in liver glycogen content. In addition, histopathology of the liver showed mild-to-moderate inflammatory reactions, severe degeneration and necrosis. Pretreatment with HD-03/ES (250, 500 and 1000 mg/kg, p.o.) showed significant and dose-dependent protection against CCl4-induced hepatic damage by normalizing serum SGPT and SGOT levels, and liver glycogen content. Furthermore, histopathology of HD-03/ES (500 and 1000 mg/kg) treated animals showed tendency toward normalization of cytoarchitecture of liver. In the antioxidant evaluation studies, HD-03/ES showed potent antioxidant activity by scavenging DPPH radicals (IC50 value = 499.4), exhibited reducing activity and also scavenging of peroxyl radical in the ORAC assay. Conclusion: These findings suggest that HD-03/ES formulation possesses significant hepatoprotective and antioxidant activities.

Antihyperglycemic and lipid lowering effect of Tectona grandis in alloxan induced diabetic rats

SUMMARY In India, Tectona grandis is traditionally used in the treatment of diabetes mellitus and lipiddisorder. In the present study, the antihyperglycemic and lipid lowering effect of ethanolic extractof bark of Tectona grandis (TG) was evaluated using alloxan induced diabetes in rats. Alloxan wasgiven at the dose of 140 mg/kg, i.p. After induction of diabetes, TG was administered for 42 daysp. o. and simultaneously different biochemical parameters like plasma glucose, liver glycogencontent, serum triglyceride, cholesterol, LDL-cholesterol and HDL-cholesterol were estimated.Diabetic control showed significant increase (P < 0.01) in plasma glucose, serum triglyceride,cholesterol, LDL-cholesterol and significant decrease (P < 0.01) in serum HDL-cholesterol andliver glycogen content. Treatment with TG showed significant reduction (P < 0.01) in plasmaglucose when compared with diabetic control. The elevated levels of serum triglyceride andcholesterol levels were significantly reduced (P < 0.01) by TG. TG treatment for 42 days showedsignificant decrease in serum LDL-cholesterol (P < 0.01) and significant increase in serum HDL-cholesterol level (P < 0.01). Moreover, diabetic control there was significant decrease in liverglycogen content which was significantly increased (P < 0.05) by treatment with TG. Hence, fromthe result obtained in the present study it can be concluded that Tectona grandis has the potentialto treat diabetes condition and associated lipid disorder.Key words: Tectona grandis; Alloxan; Antihyperglycemic; Lipid lowering; Glucose; Glycogen

Glycogen sparing effect induced by lipid supplementation in rats submitted to endurance exercise

Diversos estudos relacionam a adoção de dietas hiperlipídicas ao aumento na capacidade de utilização de lipídios e, por conseguinte, à ocorrência do efeito poupador de glicogênio. Além da maior oferta, a qualidade do lipídio oferecido é capaz de alterar sua taxa de oxidação. O objetivo deste estudo foi verificar o efeito da suplementação lipídica com diferentes tipos de óleos sobre a ocorrência do efeito poupador de glicogênio em ratos submetidos ao exercício de “endurance” (60% V 02PiCo Por 60 minutos). Os animais foram divididos em três grupos: grupo controle treinado (CT), grupo treinado suplementado com óleo de fígado de bacalhau (OFBT) e grupo treinado suplementado com óleo de palmiste (OPT). Após o exercício, o conteúdo de glicogênio muscular não diferiu significativamente entre todos os grupos (Gastrocnêmio - CT 0,31 ±0,02, OFBT 0,25 ± 0,02, OPT - 0,26 ± 0,02; Sóleo CT 0,44 ± 0,04, OFBT - 0,39 ± 0,03, OPT - 0,38 ± 0,04 mg. 100 mg' 1 de tecido úmido). O contrário foi observado no estoque hepático de glicogênio. Os grupos suplementados (OFBT 1,21 ± 0,05, OPT 1,02 ± 0,03 mg. 100 mg'1 de tecido úmido) apresentaram uma redução drástica em relação ao CT (2,12 ± 0,14 mg.100 mg' 1 de tecido úmido). Em ratos, conforme demonstrado anteriormente, a redução do conteúdo hepático de glicogênio e a subseqüente hipoglicemia constituem os fatores limitantes para o desempenho; portanto, independentemente do tipo de lipídio oferecido, os animais suplementados apresentaram menor estoque hepático de glicogênio e, conseqüentemente, essa adaptação será deletéria para o desempenho

Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1.

The purpose of the present study was to test the hypothesis that the exercise-induced increase in insulin-like growth factor binding protein (IGFBP)-1 is not always linked to a decrease in blood glucose level and to examine whether the decreasing levels of liver glycogen during exercise may be associated with the increase in IGFBP-1. Three groups of rats were submitted to a 70-min treadmill exercise. One group of rats was fed normally, and the two other groups had their food intake restricted by 50% (50% fast) the night before the experiment. One of these two 50% fasted groups of rats was infused (intravenously) with glucose throughout exercise to maintain euglycemia. Exercise in noninfused 50% fasted rats, compared with the normally fed rats, resulted in significantly lower blood glucose (minute 70) and insulin levels, significantly lower liver glycogen content, no change in IGF-I, and significantly higher increases in free fatty acid, glycerol, beta-hydroxybutyrate, and IGFBP-1. Maintenance of euglycemia during exercise in glucose-infused 50% fasted rats reduced to a large extent the decrease in insulin levels but only slightly attenuated the lipid response and the IGFBP-1 response seen in noninfused 50% fasted rats. Comparisons of all individual liver glycogen and IGFBP-1 values revealed that liver glycogen values were highly (P < 0.001) predictive of the IGFBP-1 response during exercise (R = 0.564). The present results indicate that the IGFBP-1 response during exercise is not always linked to a decrease in plasma glucose and suggest that the increase in IGFBP-1 during exercise may be related to the decrease in liver glycogen content.

Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat

The effect of oral administration of Rosmarinus officinalis L. (Lamiaceae) on CCl4-induced acute liver injury was investigated. Rats were daily treated with the plant extract at a dose of 200 mg/kg corresponding to 6.04 mg/kg of carnosol as determined by reverse phase high-performance liquid chromatography. The treatment was initiated 1 h after CCl4 administration and Rosmarinus officinalis fully prevented CCl4 effect on hepatic lipid peroxidation after 24 h of CCl4 administration. The increase in bilirubin level and alanine aminotransferase activity in plasma induced by CCl4 was completely normalized by Rosmarinus officinalis. The treatment also produced a significant recovery of CCl4-induced decrease in liver glycogen content. CCl4 did not modify the activity of liver cytosolic glutathione S-transferase (GST) compared with that of control groups. However, Rosmarinus officinalis increased liver cytosolic GST activity and produced an additional increment in plasma GST activity in rats treated with CCl4. Histological evaluation showed that Rosmarinus officinalis partially prevented CCl4-induced inflammation, necrosis and vacuolation. Rosmarinus officinalis might exert a dual effect on CCl4-induced acute liver injury, acting as an antioxidant and improving GST-dependent detoxification systems.

Effects of Hepatic Portal Infusion of Hypertonic Saline on Glucagon Response to Exercise

The present study was conducted to evaluate the influence of a hepatic portal infusion of hypertonic saline on the metabolic and hormonal responses to exercise. Adrenodemedullated male rats were studied at rest or after 30 min of treadmill exercise (26 m/min, 0% grade). Three groups of rats were infused continuously at a rate of 52 μL/min with one of the following randomly assigned conditions: hypertonic 3.6% NaCl (P3.6% NaCl) or 1.8% NaCl (P1.8% NaCl) infused into the hepatic portal vein, and hypertonic 3.6% NaCl (J3.6% NaCl) infused into the jugular vein. One group of rats received no infusion (SHAM). The infusions of hypertonic NaCl into the portal or the jugular site resulted in a significant ( p < 0.05) increase in peripheral concentration of Na +, Cl −, and osmolality at rest and after exercise. The antidiuretic hormone (ADH) concentration was significantly ( p < 0.05) increased by the P3.6% NaCl and J3.6% NaCl infusions at rest and after exercise. Exercise caused a significant ( p < 0.05). decrease in liver glycogen content, peripheral and portal plasma glycemia, and insulinemia regardless of the different types and sites of infusions. However, the peripheral glucagon response to exercise was significantly ( p < 0.05) increased only when hypertonic saline (1.8 or 3.6%) was infused into the portal vein. Portal and peripheral lactate concentrations at rest and after exercise were significantly ( p < 0.01) higher in P3.6% NaCl than in all other groups. It is concluded that a 30-min hypertonic saline infusion into the hepatic portal vein does not specifically influence the insulin response at rest and after exercise, but that glucagon response to exercise is increased by such an infusion.

Metabolic Effects of Dehydration on an Aquatic Frog, Rana Pipiens

Cellular responses to dehydration were analyzed in six organs of leopard frogs Rana pipiens. Frogs at 5 degrees C endured the loss of up to 50% of their total body water content but water contents of individual organs were strongly defended. Skeletal muscle water content was strongly affected by dehydration, dropping from 80.7% of wet mass in controls to 67.2% in frogs that had lost 50% of their total body water. However, water contents of internal organs dropped by only 3-8% of their wet masses. Water contents of all organs except skeletal muscle were fully restored by 24h of rehydration in water at 5 degrees C. Dehydration had no consistent effect on the protein content of five organs but in a sixth, the kidney, protein levels were elevated (by 60-72%) at the higher levels of dehydration and during rehydration. Dehydration led to a rapid increase in glucose concentration in the liver; compared with control values of 13 +/- 2 nmol mg-1 protein, levels were doubled by 12.2% dehydration and continued to increase to a maximum of 307 +/- 44 nmol mg-1 protein (20 mumol g-1 wet mass) in 50% dehydrated frogs. Glucose accumulation was supported by a decrease in liver glycogen content and a parallel rise in glucose 6-phosphate levels, but not in the levels of other glycolytic intermediates, confirming that glycogenolytic flux was being directed into glucose synthesis. Blood glucose levels also increased as a function of increasing dehydration, reaching values 13.8 times higher than controls, but only the kidney and brain showed a significant accumulation of glucose over the course of dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

LIVERS FROM FASTED RATS ACQUIRE RESISTANCE TO WARM AND COLD ISCHEMIA INJURY

Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold ischemia. In fact, the livers appeared to be better able to tolerate ischemia when obtained from fasted rats. Thus donor nutritional status may be an important factor for outcome of liver transplantation. Livers from fasted donors may be capable of tolerating long-term preservation better than livers from fed donors.

Effect of hepatic vagotomy on postexercise substrate levels in food-restricted rats.

The metabolic effects of a selective hepatic vagotomy (HV) were investigated at rest and immediately after a 50-min exercise period (26 m/min, 0% grade) in rats subjected to an overnight 50% food restriction. This dietary restriction reduced liver glycogen content to 50% of normal resting concentrations (2.2-2.8 g/100 g). No significant differences between HV and sham-operated rats were found in resting and exercising beta-hydroxybutyrate, glucose, glycerol, and insulin concentrations. Postexercise liver glycogen concentrations were reduced to approximately 1.0 g/100 g in both HV and sham-operated groups. This decrease was associated with significantly (P less than 0.01) lower postexercise glycogen levels in the soleus muscle of HV rats (2.6 times) along with higher plasma free fatty acid concentrations (P less than 0.01). These data provide evidence that HV combined with a progressive decrease in liver glycogen content may influence substrate regulation during exercise. They also support the concept of the existence of hepatic glucoreceptors responsive to a decrease in liver glycogen content.

Metabolism of the amino acid β-pyrazol-1-ylalanine and its parent base pyrazole

β-Pyrazol-1-yl- dl-alanine, an uncommon amino acid from plants of the Cucurbitaceae, was fed to mice. Although pyrazole is known to affect the liver enzymes UDP-glucose dehydrogenase, UDP-glucoronyl transferase and UDP-glucuronic acid pyrophosphatase, and also depresses their liver glycogen concentrations, β-pyrazol-1-ylalanine had no such effects. β-Pyrazol-1-ylalanine could not be detected in the liver of the experimental animals but was present in the urine. No other change in urinary amino acid content was observed. Studies with [ 14C]-β-pyrazol-1-yl- dl-alanine showed the administered amino acid was excreted over a 4-day period, 93% of the compound supplied was recovered. Similar recoveries were obtained with the l-enantiomer from cucumber seed. The metabolic inertness of β-pyrazol-1-ylalanine was also apparent in experiments involving subcutaneous injection of this compound. Administration of pyrazole confirmed an earlier report of resultant increased activity of liver UDP-glucose dehydrogenase and UDP-glucuronyl transferase, and of the depression of activity of liver UDP-glucuronic acid pyrophosphatase. A concomitant 40% decrease in liver glycogen content was seen. The urine contained a novel metabolite, identified as a peptide conjugate of a pyrazole derivative. Mass spectrometry and p.m.r. spectroscopy indicate that this derivative is 3,4,4-trimethyl-5-pyrazolone. The amino acid constituents are aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine and leucine. The urine of mice receiving pyrazole contained less free glycine and alanine than controls. From the results, it is concluded that pyrazole is not a catabolite of dietary β-pyrazol-1-ylalanine but to the contrary, the amino acid is essentially excreted unchanged. Formation of 3,4,4-trimethyl-5-pyrazolone from pyrazole would imply C-methylation, a process that has not been previously observed in a mammalian detoxication context.

Systemic effects of chronically administered methyl prednisolonate and methyl 17-deoxyprednisolonate.

The systemic activities of methyl prednisolonate and methyl 17-de-oxyprednisolonate (1) were studied in rats. Methyl 17-deoxyprednisolonate produced significant changes in the amount of sodium ion (decreased) and potassium ion (increased) in urine; however, methyl prednisolonate had no effect on electrolyte balance. Both methyl prednisolonate and methyl 17-deoxyprednisolonate had no effect on liver glycogen content, plasma corticosterone level and relative adrenal weight. In contrast, the parent compound prednisolone caused a significant decrease in liver glycogen content, plasma corticosterone level and relative adrenal weight.

Biochemical adaption for freezing tolerance in the wood frog,Rana sylvatica

1. The wood frog,Rana sylvatica, can survice extracellular freezing during overwintering. Under laboratory conditions freezing occurred at about −2°C and animals survived several days at −6°C. 2. Frogs accumulated glucose as a cryoprotectant; glycerol, sorbitol and other sugars were not produced. Average levels of glucose in frozen antimals were 185±40 μmol/ml in blood and 387.8±44.8, 198.3±27.3, 120.8±14.1 and 26.5±2.7 μmol/g wet weight in liver, heart, kidney and leg muscle, respectively. 3. Two methods of cold acclimation, 11 weeks at 3°C or a 1°C per day decrease in temperature from 23°C to 0°C, failed to stimulate an anticipatory rise in glucose levels. Only direct exposure to subzero temperature between 0°C and −2°C stimulated synthesis. 4. Glucose synthesis appeared to be confined to liver with glucose distributed through the blood to other tissues. Freezing exposure resulted in a decrease in liver glycogen content of over 700 μmol/g wet weight while glycogen content of other tissues was not affected. 5. Activities of 17 enzymes in liver and leg muscle were monitored in control and freezing exposed frogs. Freezing exposure increased liver phosphorylase activity by 520% from 3 to 18.6 units/g wet weight and increased phosphorylasea content from 37 to 80%. Freezing also elevated glucose-6-phosphatase activity by 140%. Activities of most other enzymes in liver increased by 30–90% with freezing exposure. Activities of phosphorylase and glucose-6-phosphatase increased in leg muscle with freezing exposure although phosphorylasea content remained at 35%. 6. Freezing exposure resulted in the accumulation of lactate in all tissues. Both total adenylates and adenylate energy charge decreased in liver during freezing. In leg muscle adenylates were unaffected but creatine phosphate reserves were depleted.

Liver glycogen in man--the effect of total starvation or a carbohydrate-poor diet followed by carbohydrate refeeding.

Liver glycogen content was determined in specimens obtained by repeated percutaneous biopsies during starvation and under various dietary conditions in 19 human subjects. During rest and following an overnight fast, there was a decrease in liver glycogen content by a mean of 0.30 mmol glucosyl units per kg wet liver tissue per min during a further 4 hours' starvation. Prolonged starvation or carbohydrate-poor normocaloric diet decreased the liver glycogen from a mean of 232 to 24–55 mmol glucosyl units per kg within 24 hours. During an additional period of up to 9 days on the carbohydrate-poor diet the liver glycogen remained at a low level. Refeeding with a carbohydrate-rich diet gave a rapid increase of the liver glycogen to supernormal values, 424–624 mmol glucosyl units per kg wet liver tissue.

The effects of starvation and of acute and chronic alloxan diabetes on myocardial substrate levels and on liver glycogen in the rat in vivo.

Cardiac levels of ATP, glycogen, glucose, glucose 6‐phosphate, fructose 6‐phosphate, fructose 1,6‐diphosphate, triose phosphates, glycerol 3‐phosphate, pyruvate, lactate, citrate, 2‐oxoglutarate, malate, acetoacetate, 3‐hydroxybutyrate and free fatty acids, as well as the liver glycogen content were determined simultaneously by instant deep‐freezing of the tissues in situ in urethanechloralose anaesthetized, normal and alloxan‐diabetic rats. In comparison to the mean values obtained in fed, normal rats the following changes in the pattern of substrate levels were found to be typical of:a) Starvation in normal rats: significant increases in citric acid cycle intermediates, in ketone bodies and in cardiac glycogen; an increase in the levels of hexose monophosphates and a decrease in fructose diphosphate, indicating inhibition of phosphofructokinase activity, and also a decrease in glycerol 3‐phosphate and triose phosphates; increase in malate/pyruvate ratio; no change in free fatty acids, ATP and pyruvate; and a most marked decrease in liver glycogen content.b) Acute alloxan diabetes: in general, changes similar to, but greater in magnitude than found in starved, normal rats, except for an unchanged 2‐oxoglutarate level; moreover, significant increases in lactate/pyruvate and 3‐hydroxybutyrate/acetoacetate ratios and a concomitant decrease in ATP were recorded. On starvation of acute diabetic rats the changes were attenuated, most significantly in regard to ketone bodies and ATP; the effect of starvation was exactly the opposite of that seen on starvation of normal rats.c) Chronic alloxan diabetes: no significant alterations except for a somewhat raised citrate level, a lowered FDP level with an associated decrease in phosphofructokinase activity, also decreased glycerol 3‐phosphate and ATP levels; liver glycogen content reduced. Starvation produced a picture of general substrate exhaustion, in which citrate, malate and the intermediates of glycolysis reached very low levels although phosphofructokinase activity was high, in association with low acetoacetate values and a decrease in even cardiac glycogen and FFA levels; liver glycogen stores were depleted.Regression analyses were carried out on the above data and it was established that the FDP/F6P ratio showed a highly significant negative correlation to cardiac citrate, but not to ATP levels, under all conditions. Furthermore, ketone‐body levels and also the lactate/pyruvate ratio showed a steep positive correlation to citrate above a critical level of 60–70 μmoles/100 g citrate, whilst the 3‐hydroxybutyrate/acetoacetate ratio was positively correlated to citrate over the entire range of concentrations. A further aspect was the demonstration of a highly significant negative correlation between cardiac citrate and liver glycogen in normal and in acute diabetic rats, and between cardiac ketone bodies and liver glycogen under all conditions; cardiac ketone bodies did not accumulate until the liver glycogen stores were depleted below a critical level of about 2000 μmoles/100 g, but then increased very steeply.

Effect of ethanol on growth and liver components in mice

The growth rate and body weight of male mice of the C 57Bl/1OJ strain maintained on 15 per cent ethanol solution for periods of one to 12 months was comparable to that of the controls. There was no difference in the liver nitrogen content. However, the liver ADH content of the ethanol groups was significantly higher and the liver glycogen content was significantly lower than that of the controls. Mice paired-fed with the ethanol groups and provided with an additional 300 mg. of sucrose daily grew at a subnormal rate and attained subnormal body and liver weights. The liver nitrogen and liver ADH level was significantly lower than that of the ethanol groups. However, the liver glycogen content of the paired-fed mice was significantly higher than that of the ethanol groups and comparable to that of the control groups. Ethanol calories can be utilized for growth, maintenance of body weight and maintenance of the nitrogen integrity of the liver. The increase in liver ADH content and the pronounced decrease in liver glycogen content are a result of ethanol, per se, rather than a result of reduction in food intake.

Body glucose as fuel for thermogenesis in the white rat exposed to cold

Various parameters of glucose metabolism were measured with C14-glucose in unanesthetized warm- and cold-acclimated rats at 30° and 6°C. Exposure of warm-acclimated rats to cold was associated with a decrease in turnover time of plasma glucose, no change in glucose pool size and space, an increase in rates of turnover and oxidation of body glucose, an increase in the ratio of the oxidation rate to the turnover rate, no change in percentage of respiratory CO2 derived from glucose oxidation, and a decrease in liver glycogen content. Approximately reversed changes were observed in cold-acclimated rats transferred from a cold to a warm environment except in the values of turnover time of plasma glucose and terminal liver glycogen content which underwent smaller changes. It is concluded that cold-induced thermogenesis in white rats, whether acclimated to warm or cold environments, is associated with an increase in carbohydrate catabolism proportionate to the increase in energy metabolism.