Tissue Glycogen Content Research Articles

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes

Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800mg/kg bw), ML (700mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

Peroxisomal proliferator-activated receptor α-b deficiency induces the reprogramming of nutrient metabolism in zebrafish.

The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa. The pparab deficiency in zebrafish reduces fatty acid β-oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator-activated receptor α (PPARα). pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown. The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology. Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator-activated receptor α (PPARα) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid β-oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPARα in metabolic homeostasis, we generated a pparab-knockout zebrafish (Danio rerio) model. The pparab mutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3-kinase/AKT pathway. In addition, pparab-deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed that pparab deletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPARα in systemic energy metabolism in fish, and this pparab-deficient zebrafish also constitutes a valuable model for investigating the functions of PPARα in mammals from comparative physiology aspects.

Seasonal and elevational variation in glucose and glycogen in two songbird species

Birds naturally maintain high glucose concentrations in the blood and tissues, even when relying on fat to meet the metabolic demands of flight or thermogenesis. One possibility is that high glucose levels might be needed to deal with these metabolic demands. Thus, we hypothesized that birds chronically exposed to colder temperatures and higher elevations have higher circulating glucose and tissue free glucose and glycogen compared to conspecifics living at warmer temperatures and lower elevations. Adult House Sparrows (Passer domesticus) and House Finches (Haemorhous mexicanus) were captured from Phoenix, AZ (340 m elevation), and Albuquerque, NM (1600 m elevation), during the summer and winter months. We measured plasma glucose, as well as free glucose and glycogen from multiple tissues. In general, high elevation and colder temperatures were associated with higher tissue glycogen and higher free glucose concentrations in the brain. These findings indicate that glucose and glycogen are subject to seasonal phenotypic flexibility as well as geographic variations that may relate to local food availability and abundance.

Parental Males of the Plainfin Midshipman Are Physiologically Resilient to the Challenges of the Intertidal Zone.

The decision of where to rear young is influenced by both the needs of offspring and the costs parents incur in certain rearing environments. Plainfin midshipman fish (Porichthys notatus) provide extended paternal care in rocky intertidal zones, where they experience regular bouts of aquatic hypoxia and air exposure during low-tide events. We investigated the physiological responses of plainfin midshipman males to three conditions for 6 h that simulate what these fish naturally experience during tidal cycles while nesting: normoxia, progressive hypoxia, or air exposure. Hypoxia- and air-exposed fish exhibited shifts in energy metabolites, driven largely by elevated lactate and glucose content and reduced glycogen content in several tissues (muscle, heart, liver, and brain), but the magnitude of these changes was relatively modest. Hematocrit increased most in air-exposed fish relative to normoxia-exposed fish, contributing to an increase in whole-blood hemoglobin concentration. Air exposure reduced swim bladder oxygen content, suggesting that internal O2 stores are drawn on during air exposure. In a second experiment, we found that aquatic surface respiration and gill ventilation frequency increased in hypoxia-exposed fish relative to normoxia-exposed fish. Overall, our results suggest that plainfin midshipman overcome the challenges of the intertidal environment through a variety of physiological strategies and exhibit little physiological disturbance in response to the fluctuating and extreme conditions created by regular low tides.

Characterization, fluctuation and tissue differences in nutrient content in the Pacific oyster ( Crassostrea gigas ) in Qingdao, northern China

The Pacific oyster (Crassostrea gigas) is one of the most important aquaculture species worldwide. Its meat quality is vital for consumer satisfaction, and nutrient content, especially glycogen, is closely associated with oyster fatness and meat colour. Fluctuations in nutrient content of short-term starvation have not been previously reported, and seasonal variation in glycogen content in different tissues has rarely been reported. In the present study, we investigated these important aspects of oyster production and found that short-term starvation (50 hr) did not significantly alter glycogen, protein or lipid content. The seasonal variation assay showed that glycogen and lipid accumulation was high in autumn and winter and that seawater temperature and protein content were inversely related to glycogen content. Glycogen content of the whole flesh was higher from January to April and was positively related to the condition index before the onset of gametogenesis. Glycogen content was higher in the gonad, labial palp and mantle compared to the gill or adductor muscle. Relative expression of genes encoding proteins involved in glycogen metabolism (glycogen synthase, glycogen phosphorylase, glycogen debranching enzyme and glycogen branching enzyme) was closely associated with the glycogen content in the corresponding tissues. Glycogen content in the gonad was regulated by glycogen metabolic and glycolysis pathway genes (6-phosphofructo kinase, phosphoglycerate kinase, pyruvate kinase, hexokinase and glucose transporters), and stored glycogen was the main energy source for gametogenesis. These findings contribute to oyster aquaculture management and glycogen improvement and expand our understanding of glycogen metabolism in oysters.

Casein fortified diet reversed the diabetes like changes induced by 4G connected mobile phone radiation in mice

Aim: Mobile phone usage is increasing day by day and has become an indispensable part of our life. However, people are constantly being exposed to the harmful electromagnetic radiation emitted from mobile phones and the remedy for the same is yet indiscernible. In our current report, we have investigated the role of a high casein diet (HCD) in ameliorating the pancreatic and hepatotoxic effects of mobile phone radiation. Materials and Methods: Mice (n=24) were divided into four groups and maintained as control groups (Gr-A: normal diet; Gr-D: HCD) and mobile phone radiation (SAR value: 1.5 W/ kg at 1g body wt.) exposed groups, irradiated for 3 hours/ day for 90 days (Gr-B: normal diet; Gr-C: HCD). The normal diet contained 5% casein while HCD contained 20% casein. After the tenure of radiation exposure terminates, animals were sacrificed; the pancreatic, hepatic tissues, and blood were collected for the histology and serum isolation respectively. Periodic acid- Schiff staining was performed to assess the glycogen content of hepatic tissue and hematoxylin-eosin staining for general histological analysis. The serum was used to estimate the fasting glucose level. Observations: Increased fasting serum glucose level and shrunken pancreatic islets on radiation exposure may indicate the diabetes progression. Loss of glycogen storage capacity by the liver was observed in radiation exposed group which are suggestive of compromised hepatic functions. Histo-architectural analysis of the liver revealed severely distorted hepatic cells with prominent occurrences of karyorrhexis and karyolysis, irregular and enlarged sinusoidal spaces upon radiation exposure. HCD countermanded these abnormal manifestations of the electromagnetic radiation to a considerable extent. Inference: Thus, electromagnetic radiation from the mobile phone may be responsible for the impairment of glucose metabolism and thereby enhancing the progression of diabetes in mice. In contrast, HCD was prudent in combating these degenerative alterations of mobile phone radiation.

Transgenerational biochemical effects of seawater acidification on the Manila clam (Ruditapes philippinarum)

Ocean acidification can negatively impact marine bivalves. Pivotal to projecting their fate is the ability to acclimate and adapt to shifts in seawater chemistry. Transgenerational plasticity enables marine bivalves to acclimate, yet the underlying mechanisms at different levels of biological organization remain poorly understood. Here, we performed a transgenerational experiment to understand biochemical responses of the Manila clam, Ruditapes philippinarum, following exposure to moderately reduced seawater pH (from 8.1 to 7.7). Activities of tissue calcification-relevant enzymes, such as carbonic anhydrase (CA), acid phosphatase (ACP) and alkaline phosphatase (ALP), energy-metabolizing enzymes, such as Na+/K+-ATPase (NKA) and Ca2+/Mg2+-ATPase (CMA), as well as tissue energy reserves (glycogen, lipid and protein) were assayed. With decreasing seawater pH, adult R. philippinarum exhibited significantly increased CA activity, and especially the clams with a history of transgenerational exposure displaying significantly higher CA activity than those spawned from parents exposed to ambient seawater pH. Yet, ACP and ALP activities remained unaffected. Transgenerational exposure to reduced seawater pH led to significant increases of NKA activity, while no transgenerational response of CMA activity was observed. Tissue glycogen and lipid contents were significantly depleted under acidified conditions regardless of transgenerational exposure. Yet, transgenerational alleviation in the net protein degradation was found. These findings suggest that our current understanding of transgenerational responses is still limited by the achievable time-window possible in the laboratory. While the energetic budget is lower under acidified conditions, there is no evidence of transgenerational recovery in term of energetic budget. Therefore, this work demonstrates that the critical basis of ocean acidification resilience can most likely be explained in energetic terms.

Exposure to Elevated Concentrations of Major Ions Decreases Condition Index of Freshwater Mussels: Comparison of Metrics

Energy storage is critical for gametogenesis and successful spawning in bivalve mollusks. However, it often is overlooked as an endpoint in toxicological studies of freshwater mussels. Energy storage can be assessed through direct measurement of energy substrates or the use of the condition index (CI) as an indicator of overall nutritional status. Our study focused on the CI of adult Lampsilis fasciola exposed to treatment conditions designed to mimic the Powell River (Virginia, USA), which historically supported an exceptionally diverse freshwater mussel community. Coal mining operations have impacted the upper Powell River, and low-flow specific conductance frequently exceeds 900 µS/cm. We used four treatments in a full-factorial design to evaluate mussel responses to diluted pond water (control), simulated Powell River water, control sediment, and Powell River sediment. We measured glycogen content of mantle tissue and CI and compared several CI metrics. Exposure to simulated Powell River water caused a significant decrease in several CI metrics compared to control water. There was no effect of sediment type, nor was there any effect of sex; both males and females lost body mass in simulated Powell River water. However, males had significantly lower glycogen content of mantle tissue, indicating females likely were using other sources of energy to compensate for salinity stress. Comparison of CI metrics demonstrated that dissection was necessary to discern the effect of major ions on energy storage and that the use of tissue weight (g)/shell cavity capacity (g) had lower variability than tissue weight (g)/shell cavity volume (mL). The observed decrease in CI of adult L. fasciola after exposure to elevated concentrations of major ions has implications for maintaining mussel populations in the Powell River and in other rivers with rapidly increasing salinity.

Regulating the Warburg effect on metabolic stress and myocardial fibrosis remodeling and atrial intracardiac waveform activity induced by atrial fibrillation

Atrial fibrillation (AF) is associated with metabolic stress and induces myocardial fibrosis reconstruction by increasing glycolysis. One goal in the treatment of paroxysmal AF (p-AF) is to improve myocardial fibrosis reconstruction and myocardial metabolic stress caused by the Warburg effect. Adopted male canine that rapid right atrial pacing (RAP) for 6 days to establish a p-AF model. The canines were pre-treated with phenylephrine (PE) or dichloroacetic acid (DCA) before exposure to p-AF or non-p-AF. P-wave duration (Pmax), minimum P-wave duration (Pmin), P wave dispersion (PWD), atrial effective refractory period (AERP) and AERP dispersion (AERPd) were measured in canine atrial cardiomyocytes. Pyruvate dehydrogenase kinase-1 (PDK-1), PDK-4, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH), citrate synthase (CS), isocitrate dehydrogenase (IDH), and matrix metalloproteinase 9 (MMP-9) were evaluated by western blotting and reverse transcription polymerase chain reaction (RT-PCR), content of adenosine monophosphate (AMP), adenosine triphosphate (ATP), lactic acid and glycogen, and activity of LDHA, PDK-1 and PDK-4 were evaluated by enzyme-linked immunosorbent assay (ELISA), myocardial tissue glycogen content was evaluated by PAS, myocardial fibrosis remodeling was evaluated by hematoxylin and eosin (H&E) and Masson staining. Our findings demonstrated that p-AF increases the Warburg effect-related metabolic stress and myocardial fibrosis remodeling by increasing the expression and activity of PDK-1, PDK-4, and LDHA, content of AMP and lactic acid, and the ratio of AMP/ATP and decreasing the expression of PDH, CS, and IDH, and glycogen content. In addition, p-AF can induce cardiomyocyte fibrosis remodeling and increase MMP-9 expression, and p-AF also increases atrial intracardiac waveform activity by prolonging Pmax, Pmin, PWD, and AERPd and shortening AERP. PDK isoforms agonists (PE) produce a similar p-AF pathological effect and can produce synergistic effects with p-AF, further increasing Warburg effect-related metabolic stress, myocardial fibrosis remodeling, and atrial intracardiac waveform activity. In contrast, the use of PDK-specific inhibitors (DCA) completely reverses these pathophysiological changes induced by p-AF. We demonstrate that p-AF can induce the Warburg effect in canine atrial cardiomyocytes and significantly improve p-AF-induced metabolic stress, myocardial fibrosis remodeling, and atrial intracardiac waveform activity by inhibiting the Warburg effect.

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.

Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer

BackgroundRadiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear.MethodsWe used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdcscid/J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation.ResultsWe report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ–H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure.ConclusionOur results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity.

Biochemical and Histopathological study Of The Proteinaceous Compounds Separated From Aqueous Extract Of Marus Albul L. Fruit in alloxan diabetic mice

This work was concerned with isolating and molecular weight determination of the proteinous compounds isolated from the cold and boiled aqueous extract of Marus Albal L. using different biochemical techniques . Also this study indicated the effect of the proteinaceous compounds Ac, Bc and Ab, Bb on some biochemical parameters including glucose, cholesterol and total lipids levels in blood serum and glycogen content in liver tissues in normal and diabetic mice . A single intraperitoneal injection of these isolated compounds with a dose of 75 mg / kg body weight was used .As well as pancreas were removed and stained with H and E of pancreatic sections. Results indicated that intraperitoneal injection of insulin and all the proteinaceous compounds Ac , Bc and Ab, Bb obtained by gel filtration chromatography from the plant used had hypoglycemic effect on serum glucose level in normal and diabetic mice. The rate of decrease was from (18.2) to (43.7) % in the normal and form (29.57) to (50.20) % in the diabetic mice respectively. While compounds (Bb) showed a negligible to an increasing effect (3.91) % in the normal and (7.99)% in the diabetic mice. Also the highest decrease was obtained for compound (Ac), this decrease were (16.8 )% and (15.73) % for serum cholesterol levels in the normal and the diabetic mice respectively .As well as the highest decrease was obtained for compound (Ac) , this decrease were(23.62) % and (28.88) % for serum total lipids levels in the normal and the diabetic mice respectively. Also a decrease between (5.8 , 14.1) % and (6.4 , 12.9) % glycogen content in liver tissues was obtained when the normal and in the diabetic mice respectively were injected intraperitoneally by the proteinaceous compounds Ac, Bc and Ab , Bb from plants used. Finally alloxan induced diabetic mice group, the endocrine pancreas histologically showed decreased in the size and number of Langerhans islets with vacuolar degeneration and necrosis of almost all cell in the atrophied islets as compared with control group. The histomorphometic study of the pancreas of the treated group didn't show a significant change of the pancreatic tissue.

Hypoglycemic activity and mechanism of the sulfated rhamnose polysaccharides chromium(III) complex in type 2 diabetic mice

The sulfated rhamnose polysaccharides found in Enteromorpha prolifera belong to a class of unique polyanionic polysaccharides with high chelation capacity. In this study, a complex of sulfated rhamnose polysaccharides with chromium(III) (SRPC) was synthesized, and its effect on type 2 diabetes mellitus (T2DM) in mice fed a high-fat, high-sucrose diet was investigated. The molecular weight of SRPC is 4.57 kDa, and its chromium content is 28 μg/mg. Results indicated that mice treated by oral administration of SRPC (10 mg/kg and 30 mg/kg body mass per day) for 11 weeks showed significantly improved oral glucose tolerance, decreased body mass gain, reduced serum insulin levels, and increased tissue glycogen content relative to T2DM mice (p < 0.01). SRPC treatment improved glucose metabolism via activation of the IR/IRS-2/PI3K/PKB/GSK-3β signaling pathway (which is related to glycogen synthesis) and enhanced glucose transport through insulin signaling cascade–induced GLUT4 translocation. Because of its effectiveness and stability, SRPC could be used as a therapeutic agent for blood glucose control and a promising nutraceutical for T2DM treatment.

Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2',3,3'-Tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice.

Protein tyrosine phosphatase 1B (PTP1B) is a widely confirmed target of the type 2 diabetes mellitus (T2DM) treatment. Herein, we reported a highly specific PTP1B inhibitor 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (compound 1), which showed promising hypoglycemic activity in diabetic BKS db mice. With the IC50 value of 2.4 μM, compound 1 could directly bind to the catalytic pocket of PTP1B through a series of hydrogen bonds. Surface plasmon resonance analysis revealed that the target affinity [KD (equilibrium dissociation constant) value] of compound 1 binding to PTP1B was 2.90 μM. Moreover, compound 1 could activate the insulin signaling pathway in C2C12 skeletal muscle cells. We further evaluated the long-term effects of compound 1 in diabetic BKS db mice. Notably, oral administration of compound 1 significantly reduced the blood glucose levels of diabetic mice with increasing insulin sensitivity. In addition, the dyslipidemia of diabetic mice was also significantly improved by compound 1 gavage. The histological experiments showed that compound 1 treatment significantly ameliorated the disordered hepatic and pancreatic architecture and increased the glycogen content in the liver tissues as well as improved the insulin secretion function of pancreas. Taken together, our results manifested that the natural product compound 1 was a highly specific PTP1B inhibitor, which could activate insulin signaling pathway and ameliorate hyperglycemia and dyslipidemia in diabetic BKS db mice.

Mito-TEMPO, a mitochondria-targeted antioxidant, prevents N-nitrosodiethylamine-induced hepatocarcinogenesis in mice

BackgroundOxidative stress and mitochondrial dysfunction play a significant role in hepatocarcinogenesis. Mitochondria are source organelle as well as target for free radicals. The oxidative damage to mitochondria can be prevented by mitochondria-targeted antioxidant, mito-TEMPO. However, its efficacy in prevention of hepatocellular carcinoma has not been investigated so far. MethodsMurine model of hepatocarcinogenesis was developed by intraperitoneal administration of N-nitrosodiethylamine to male BALB/c mice. Mito-TEMPO was administered intraperitoneally at weekly intervals, till the completion of the study. The tumours were histopathologically analysed and anti-cancer efficacy of mito-TEMPO was evaluated in terms of survival index, tumour incidence, tumour multiplicity and tumour dielectric parameters. The antioxidant defence status and molecular composition of tumours were assessed. Gap junctions and gap-junctional intercellular communication (GJIC) were studied using ELISA, IHC and Lucifer yellow assay. ResultsMito-TEMPO treatment increased survival of animals by 30%, decreased tumour incidence (25%) and tumour multiplicity (39%). The dielectric parameters of tumours in Mito-TEMPO group were indicative of retarded carcinogenesis. Mito-TEMPO administration normalized mean saturation levels in phospholipids and improved glycogen content of the hepatic tissue. Gap junctions and GJIC which were severely impaired in hepatocarcinogenesis, improved after mito-TEMPO treatment. ConclusionMito-TEMPO was effective in combating hepatocarcinogenesis.

The Effects of Ergosta-7,9(11),22-trien-3β-ol from Antrodia camphorata on the Biochemical Profile and Exercise Performance of Mice.

Antrodia camphorata (AC) is a rare and unique mushroom that is difficult to cultivate. Previous studies have demonstrated the bioactivity of the compound Ergosta-7,9(11),22-trien-3β-ol (EK100) from AC in submerged culture. The purpose of this study is to evaluate the potential beneficial effects of EK100 on fatigue and ergogenic functions following physiological challenge. Male ICR (Institute of Cancer Research) mice were randomly divided into three groups (n = 8 per group) and orally administered EK100 for six weeks at 0 (Vehicle), 10 (EK100-1X), and 20 (EK100-2X) mg/kg/day. The six-week Ek100 supplementation significantly increased grip strength (p = 0.0051) in trend analysis. Anti-fatigue activity was evaluated using 15-min. acute exercise testing and measuring the levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) after a 15-min. swimming exercise. Our results indicate that AC supplementation leads to a dose-dependent decrease in serum lactate, ammonia, BUN, and CK activity after exercise and significantly increases serum glucose and glycogen content in liver tissues. Biochemical and histopathological data demonstrated that long term daily administration of EK100 for over six weeks (subacute toxicity) was safe. EK100’s anti-fatigue properties appear to be through the preservation of energy storage, increasing blood glucose and liver glycogen content, and decreasing the serum levels of lactate, ammonia, BUN, and CK. EK100 could potentially be used to improve exercise physiological adaptation, promote health, and as a potential ergogenic aid in combination with different nutrient strategies.

Evaluation of biochemical mechanisms of anti-diabetic functions of Anisomeles malabarica

Anisomeles malabarica (AM) is an aromatic plant traditionally used for the treatment of diabetes mellitus in India. Following bioassay guided fractionation, we recently identified an active fraction of AM (AMAF, with potential mix of active principles) that showed significant antihyperglycemic and antihyperlipidemic activities. In addition, AMAF treatment improved insulin levels. However, the biochemical mechanism/s through which AMAF demonstrates the antidiabetic effects is largely unknown. Based on its beneficial effects we investigated the biochemical mechanism of the anti-diabetic activity of A.malabarica active fraction (AMAF) in streptozotocin (STZ) induced diabetic rats. Streptozotocin induced diabetic rats were treated with AMAF (50 mg AMAF/kg/day) for 30 days and alterations in the body weights, glycogen and protein content of tissues, functional markers of hepatic and renal tissues, carbohydrate metabolic enzymes and their genes expression were evaluated. Lipid peroxides levels and activities of antioxidant enzymes of hepatic and renal tissues were also measured. The AMAF treatment resulted in increase in body weights, hepatic and renal protein and tissue glycogen levels in diabetic treated rats compared to diabetic rats. In addition, the treatment improved activities of carbohydrate metabolic enzymes, antioxidant enzymes and, liver and renal functional markers in the AMAF treated diabetic rats. Gene expressions of key carbohydrate metabolic enzymes/factors glucokinase, glucose transporter protein (GLUT-2) and phosphoenolpyruvate carboxykinase (PEPCK) were also normalized up on AMAF treatment in diabetic rats. Our studies indicate that the isolated active fraction of AM (AMAF) from the leaves of A.malabarica positively regulated the glucose homeostasis and oxidative stress through carbohydrate metabolism and antioxidant enzyme activities respectively in hepatic and renal tissues.

Therapeutic effect of mesenchymal stem cells and insulin producing cells on the liver of streptozotocin-induced diabetic mice

Diabetes mellitus (DM) is a major medical concern due to its high prevalence and potential deleterious effect on the patient physical and psychological state. Diabetes is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. Insulin deficiency, in turn, leads to chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism. The liver is an insulin-guided organ as its behavior changes depending on the level of insulin in the blood. To stimulate diabetes, mice were injected intraperitoneally with a single dose of STZ (160 mg/kg B.W). In the present study, we investigated the effect of intravenous injection of mesenchymal stem cells obtained from 6-8 weeks adult CD-1 mice on the liver of streptozotocin-induced diabetic mice. Liver tissue glycogen content and the extent of liver degeneration were assessed using histological and ultra-structural studies.

Probiotic Lactobacillus gasseri SBT2055 improves insulin secretion in a diabetic rat model

The probiotic Lactobacillus gasseri SBT2055 (LG2055) has a protective effect against metabolic syndrome in rats and humans. Metabolic syndrome increases the risk of type 2 diabetes mellitus. In this study, Goto-Kakizaki rats were used as a diabetic model and fed diets containing LG2055-fermented or nonfermented skim milk for 4 wk. Indices of diabetes such as blood glucose levels, serum glucagon levels, plasma levels of insulin, C-peptide, and glucagon-like peptide-1, tissue glycogen contents, and pancreatic mRNA levels were measured. The plasma C-peptide levels and pancreatic mRNA levels of insulin genes (Ins1 and Ins2) and Pdx1 (a transcriptional factor of insulin genes) were increased in LG2055 diet-fed rats. The increase in insulin secretion corresponded to an improvement in serum and pancreatic inflammatory status, associated with decreases in serum levels of serum amyloid P and pancreatic levels of granulocyte colony-stimulating factor. Insulin resistance in Goto-Kakizaki rats was ameliorated by increased glycogen storage in the liver and quadriceps femoris muscles and decreased serum free fatty acid levels. This improvement may be related to the increased cecal production of short-chain fatty acids. In conclusion, dietary LG2055 improved insulin secretion in diabetic rats by improving the inflammatory status in the pancreas and serum.

Benfotiamine, a Lipid-Soluble Analog of Vitamin B1, Improves the Mitochondrial Biogenesis and Function in Blunt Snout Bream (Megalobrama amblycephala) Fed High-Carbohydrate Diets by Promoting the AMPK/PGC-1β/NRF-1 Axis.

This study evaluated the effects of benfotiamine on the growth performance and mitochondrial biogenesis and function in Megalobrama amblycephala fed high-carbohydrate (HC) diets. The fish (45.25 ± 0.34 g) were randomly fed six diets: the control diet (30% carbohydrate, C), the HC diet (43% carbohydrate), and the HC diet supplemented with different benfotiamine levels (0.7125 (HCB1), 1.425 (HCB2), 2.85 (HCB3), and 5.7 (HCB4) mg/kg) for 12 weeks. High-carbohydrate levels remarkably decreased the weight gain rate (WGR), specific growth rate (SGR), relative feed intake (RFI), feed conversion ratio (FCR), p-adenosine monophosphate (AMP)-activated protein kinase (AMPK)α/t-AMPKα ratio, peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β) and nuclear respiratory factor-1 (NRF-1) protein expression, complexes I, III, and IV activities, and hepatic transcriptions of cytochrome b (CYT-b) and cytochrome c oxidase-2 (COX-2), whereas the opposite was true for plasma glucose, glycated serum protein, advanced glycation end product and insulin levels, tissue glycogen and lipid contents, hepatic adenosine triphosphate (ATP) and AMP contents and ATP/AMP ratio, complexes V activities, and the expressions of AMPKα-2, PGC-1β, NRF-1, mitochondrial transcription factor A (TFAM), mitofusin-1 (Mfn-1), optic atrophy-1 (Opa-1), dynamin-related protein-1 (Drp-1), fission-1 (Fis-1), mitochondrial fission factor (Mff), and ATP synthase-6 (ATP-6). As with benfotiamine supplementation, the HCB2 diet remarkably increased WGR, SGR, tissue glycogen and lipid contents, AMP content, p-AMPKα/t-AMPKα ratio, PGC-1β and NRF-1 levels, complexes I, III, IV, and V activities, and hepatic transcriptions of AMPKα-2, PGC-1β, NRF-1, TFAM, Mfn-1, Opa-1, CYT-b, COX-2, and ATP-6, while the opposite was true for the remaining indicators. Overall, 1.425 mg/kg benfotiamine improved the growth performance and mitochondrial biogenesis and function in fish fed HC diets by the activation of the AMPK/PGC-1β/NRF-1 axis and the upregulation of the activities and transcriptions of mitochondrial complexes as well as the enhancement of mitochondrial fusion coupled with the depression of mitochondrial fission.