Glucose 6-phosphatase Activity Research Articles

Dose-dependent alteration in hepatic and cerebral glucose metabolism following exposure to polystyrene microplastic in Wistar rats

Background: Recently, microplastics (MPs) with dimensions less than 5 mm have gained more attention due to their adverse impact on the environment and living creatures. Polystyrene (PS) particle is a key element of primary microplastics, which are causing numerous health issues such as interruption of energy metabolism, oxidative stress, neurotoxicity, immunotoxicity, digestive gland disorders, reproductive disruption, and genotoxicity in marine living organisms. Method: Alteration in carbohydrate metabolism was evaluated in male Wistar rats (six weeks of age) after four weeks of oral exposure to polystyrene microplastic (PS-MP) at three different doses (0.5mg/L, 5mg/L and 50 mg/L via drinking water). Results: Polystyrene exposure caused a significant decrease in blood glucose, liver glycogen, and pyruvic acid content in liver and cerebral tissue. Free amino nitrogen content significantly altered in the liver and cerebrum in a dose-specific manner. The LDH activity was found to be decreased in the liver, whereas it increased in the cerebral cortex of rats in a dose-responsive fashion. Enzymes like glucose 6-phosphatase, GOT, GPT, and succinate dehydrogenase activities demonstrated differential effects on the liver and cerebrum of rats in terms of energy metabolism. Conclusion: It is suggested that sub-acute polystyrene exposure significantly perturbs glucose metabolism by inducing hypoglycemia associated with decreased glycolysis and increased TCA cycle enzyme function in rat liver in a dose-dependent manner. Gluconeogenesis is also affected differentially by metabolic adjustment in the studied organs.

Polysaccharide from walnut green husk alleviates liver inflammation and gluconeogenesis dysfunction by altering gut microbiota in ochratoxin A-induced mice

Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Galp-(1→, α-D-Galp (1→, and →2)-α-L-Rhap-(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota.

THE EFFECT OF BOLDINE ON BODY COMPOSITION AND CARBOHYDRATE METABOLISM IN OBESE MICE

Boldine is an alkaloid widely found in boldo leaves. Recent studies have determined itspotential effect on glycemic and lipidemia control. Because of this, the objective of this workwas to evaluate the effect of boldine on body composition and carbohydrate metabolism inobese mice induced by a high-calorie diet. 21-day-old male Swiss mice were divided intocontrol (standard diet), cafeteria (high-calorie diet) and treatment (boldine 20mg/Kg) groups.After 90 days of treatment, the animals were euthanized, the liver was collected, andepididymal, retroperitoneal, mesenteric and brown fats were weighed. Obese animalsincreased body and fat weight, but boldine treatment decreased body weight (17%) andabdominal circumference (15%) and reduced retroperitoneal (66%) and mesenteric (33%) fatweight. Obesity altered the activity of glucokinase and glucose 6-phosphatase in the liver.However, the treatment decreased glucose 6-phosphatase activity (30%) and increasedglucokinase activity (43%). We conclude that boldine can be a potential preparation for themanagement and treating obesity.

Liver Glucose-6 Phosphatase Activity is Inhibited by Refeeding in Rats

This study was conducted to determine whether inhibition of hepatic glucose-6 phosphatase is involved in the mechanism of suppression of hepatic glucose production during the postprandial period. We studied the time course of changes in the enzyme activity by refeeding food-deprived rats with nonpurified diet. The Vmax of the enzyme, assayed in homogenates from livers freeze-clamped in situ in anesthetized 48-h unfed rats (12.3 ± 0.15 U/g wet liver, mean ± SEM, n = 6) was progressively decreased upon refeeding: 11.1 ± 0.5, 8.5 ± 0.4 and 7.9 ± 0.5 U/g, in rats refed for 90, 180 (P < 0.01) and 360 min (P < 0.01), respectively. The Km of the enzyme was not affected by refeeding. No inhibition of the enzyme was observed in microsomes purified from these homogenates, suggesting a metabolite-induced inhibition mechanism. To assess the role of insulin in the inhibition, we assayed the glucose-6 phosphatase activity in similarly processed liver homogenates from food-deprived rats perfused with insulin at physiological and supraphysiological concentrations, whereas plasma glucose was maintained at the basal level by adapted glucose perfusion (euglycemic clamps). No inhibition of glucose-6 phosphatase was found under these conditions, suggesting that insulin cannot by itself account for the inhibition observed in the refeeding experiments. These data constitute the first demonstration of the inhibition of glucose-6 phosphatase activity during the postprandial period.

Effects of Dietary Carbohydrate Sources on Growth Performance, Glucose Metabolism, and Digestive Enzyme Activity of Litopenaeus vannamei

This study evaluated the effects of different sources of dietary carbohydrates on the growth, antioxidant capacity, and digestive enzyme activity, and carbohydrate metabolic enzyme activity of Litopenaeus vannamei were evaluated. The experimental diets, including glucose, sucrose, potato starch, corn starch, and wheat starch, were fed to L. vannamei for 35 days. We found that shrimp fed on corn starch and wheat starch grew better, whereas shrimp fed on wheat starch showed the highest digestive enzyme activity. In addition, the starch group showed higher total superoxide dismutase (T-SOD) activity and lower malondialdehyde (MDA) content. The glucose, sucrose, starch, and corn starch fed shrimp showed significantly higher levels of hepatopancreatic hexokinase (HK), whereas those fed on glucose and potato starch also showed significantly higher levels of hepatopancreatic phosphofructokinase (PFK) activity. The activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) were higher in shrimp fed on glucose, whereas higher fructose 1,6-bisphosphatase (FBPase) activity was observed in shrimp fed on wheat starch, glucose, and sucrose. The insulin content of shrimp in the glucose group and potato starch group was higher, whereas that of the glucose group was higher than that of the potato starch group. In brief, the addition of wheat starch to the diet plays a positive role in the growth, glycolysis, gluconeogenesis, and antioxidant activity of shrimp, and is a promising choice for juvenile shrimp culture.

The metabolic and toxic acute effects of phloretin in the rat liver

The current study sought to evaluate the acute effects of phloretin (PH) on metabolic pathways involved in the maintenance of glycemia, specifically gluconeogenesis and glycogenolysis, in the perfused rat liver. The acute effects of PH on energy metabolism and toxicity parameters in isolated hepatocytes and mitochondria, as well as its effects on the activity of a few key enzymes, were also evaluated. PH inhibited gluconeogenesis from different substrates, stimulated glycogenolysis and glycolysis, and altered oxygen consumption. The citric acid cycle activity was inhibited by PH under gluconeogenic conditions. Similarly, PH reduced the cellular ATP/ADP and ATP/AMP ratios under gluconeogenic and glycogenolytic conditions. In isolated mitochondria, PH inhibited the electron transport chain and the FoF1–ATP synthase complex as well as acted as an uncoupler of oxidative phosphorylation, inhibiting the synthesis of ATP. PH also decreased the activities of malate dehydrogenase, glutamate dehydrogenase, glucose 6-phosphatase, and glucose 6-phosphate dehydrogenase. Part of the bioenergetic effects observed in isolated mitochondria was shown in isolated hepatocytes, in which PH inhibited mitochondrial respiration and decreased ATP levels. An aggravating aspect might be the finding that PH promotes the net oxidation of NADH, which contradicts the conventional belief that the compound operates as an antioxidant. Although trypan blue hepatocyte viability tests revealed substantial losses in cell viability over 120 min of incubation, PH did not promote extensive enzyme leakage from injured cells. In line with this effect, only after a lengthy period of infusion did PH considerably stimulate the release of enzymes into the effluent perfusate of livers. In conclusion, the increased glucose release caused by enhanced glycogenolysis, along with suppression of gluconeogenesis, is the opposite of what is predicted for antihyperglycemic agents. These effects were caused in part by disruption of mitochondrial bioenergetics, a result that should be considered when using PH for therapeutic purposes, particularly over long periods and in large doses.

Морфофункціональні зміни паренхіми печінки щурів при введенні L-триптофану

The morphofunctional changes of the liver parenchyma of male Wistar rats after administration of L-tryptophan were investigated. Experimental rats in addition to the standard diet received L-tryptophan at a dose of 80 mg/kg. The duration of the experiment was 28 days. Histological preparations were made from liver tissue according to standard methods. Morphometry was performed on digital images using the computer program “Image J”. The activity of hepatic aminotransferases and albumin concentration were determined in serum by biochemical methods; in liver homogenates determined glucose-6-phosphatase activity and triglyceride concentration; in the suspension of hepatocyte mitochondria determined succinate dehydrogenase activity and protein concentration. Multifrequency bioimpedancemetry was used to assess the biophysical properties of the liver. It was found that the administration of L-tryptophan leads to an increase in the nuclear-cytoplasmic ratio (19%), the number of binuclear hepatocytes (81%), and the relative area of the sinusoid (17%). Aspartate aminotransferase activity decreased in serum of experimental rats and albumin concentration increased. In the homogenate of the liver of these animals, the activity of glucose6-phosphatase and the concentration of triglycerides decreased. Succinate dehydrogenase activity and protein concentration in the hepatocyte mitochondrial suspension increased by 35% and 32%, respectively. The method of multifrequency bioimpedancemetry revealed an increase in the ability of the liver tissue of experimental rats to polarize, namely to increases in reactivity. That is, the administration of L-tryptophan is accompanied by the appearance of morphological, biochemical, and biophysical signs of increased synthetic and regenerative activity of the rat liver parenchyma.

Cannabis sativa L. protects against oxidative injury in kidney (vero) cells by mitigating perturbed metabolic activities linked to chronic kidney diseases

Ethnopharmacological relevanceCannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases. AimsThe protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines. MethodsFixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO4 for 30 min, following pretreatment with C. sativa extracts for 25 min. Normal control consisted of Vero cells not treated with the extracts and/or FeSO4, while untreated (negative) control consisted of cells treated with only FeSO4. ResultsMTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 μg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts. ConclusionThese results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.

Cannabidiol improves glucose utilization and modulates glucose-induced dysmetabolic activities in isolated rats' peripheral adipose tissues

Reduced glucose uptake and utilization, with concomitant lipolysis in adipose tissues has been linked to the pathogenesis of obesity and its complications. The present study investigated the effect of cannabinoid-stimulated glucose uptake on redox imbalance, glucose and lipid metabolisms, as well as cholinergic and purinergic dysfunctions in isolated rats’ adipose tissues. Freshly Isolated rats’ adipose tissues were incubated with glucose and different concentrations of cannabidiol for 2 h at 37 °C. The negative control consisted of incubation without cannabidiol, while normal control consisted of incubations without glucose and/or cannabidiol and Metformin served as the standard drug. Cannabidiol caused an increase in adipose-glucose uptake, with concomitant elevation of glutathione, triglyceride level, superoxide dismutase, catalase and 5′nucleoidase activities. It also caused suppression in malondialdehyde and cholesterol levels, acetylcholinesterase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase, glycogen phosphorylase, and lipase activities. In silico studies revealed a strong molecular interaction of cannabidiol with adipose triglyceride lipase, hormone-sensitive lipase, and monoglyceride lipase. These results indicate that cannabidiol-enhanced glucose uptake in adipose tissues is associated with enhanced antioxidative activities, concomitant modulation of cholinergic and purinergic dysfunctions, and improved glucose – lipid homeostasis.

Metabolic Energy Insufficiency in Mice Kidney following Short-term Exposure to Lead: An In-vivo Study

Background: Metabolic stress is one of the risk factors of lead-induced functional abnormalities of the tissue. The present study aimsat determining the effect of lead on certain energy metabolic profiles in renal tissue of mice.Method: Swiss albino mice were exposed to Pb by gavages at a 5mg/kg body weight dose for 30 days. After treatment, urinary glucose,glucose 6-phosphatase, lactate dehydrogenase, TCA cycle enzymes, different proteolytic enzyme activities, total, acidic, basic and neutralproteins, protein carbonyl content, glyceraldehyde 3-phosphate dehydrogenase activity, tissue Pb deposition and renal morphologywere examined.Results: Lead exposure resulted in glycosuria and decreased glucose 6-phosphatase activity in the kidney, whereas the lactatedehydrogenase activity was increased in that tissue. The malate dehydrogenase and succinate dehydrogenase activities were stimulatedby Pb, whereas the glyceraldehyde 3-phosphate dehydrogenase activity was inhibited. Degradation of tissue protein was accompaniedwith enhanced protein carbonylation. Significant changes in trypsin, cathepsin and pronase activities were noted. Decreased aminoacid nitrogen in kidney was associated with altered transaminase activity. Additionally, fatty infiltration was observed in associationwith accumulation of elemental lead.Conclusion: It is suggested that sub-acute Pb exposure modulated certain enzymes and intermediates of major energy metabolismpathways in the renal tissue of mice to establish an adaptive mechanism against metabolic distress.

Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice

BackgroundThe relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. Materials and MethodsCirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. ResultsAfter BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. ConclusionsIn different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.

Cannabis sativa L. Mitigates Oxidative Stress and Cholinergic Dysfunction; and Modulates Carbohydrate Metabolic Perturbation in Oxidative Testicular Injury

The therapeutic potentials of Cannabis sativa L. on oxidative-induced testicular dysfunction were investigated in isolated testes of male albino rats. C. sativa leaves were subjected to sequential extraction to yield the hexane, dichloromethane (DCM), and ethanol extracts. Oxidative injury was induced by incubating testicular tissue homogenate with 0.1 mM FeSO4 for 30 min at 37 °C. Treatment was done by incubating the tissues with C. sativa extracts and 0.1 mM FeSO4 under same conditions. Induction of oxidative injury led to significant (p < 0.05) depleted levels of glutathione, superoxide dismutase, catalase, and ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activities, while elevating malondialdehyde and nitric oxide levels, acetylcholinesterase, ATPase, glucose 6-phosphatase, fructose 1,6-biphosphatase, and amylase activities. These levels and activities were significantly (p < 0.05) reversed following treatment with the extracts. The extracts also displayed cytotoxic effect against human DU-145 prostate cancer cells. These results indicate the protective potentials of C. sativa extracts against oxidative-mediated testicular injury as shown by their ability to attenuate testicular oxidative stress, and modulate cholinergic and purinergic activities, while suppressing testicular carbohydrate dysmetabolism.

ADP-dependent glucose/glucosamine kinase from Thermococcus kodakarensis: cloning and characterization

The genome sequence of Thermococcus kodakarensis contains an open reading frame, TK1110, annotated as ADP-dependent glucokinase. The encoding gene was expressed in Escherichia coli and the gene product, TK-GLK, was produced in soluble and active form. The recombinant enzyme was extremely thermostable. Thermostability was increased significantly in the presence of ammonium sulfate. ADP was the preferred co-factor for TK-GLK, which could be replaced with CDP but with a 60% activity. TK-GLK was a metal ion-dependent enzyme which exhibited glucokinase, glucosamine kinase and glucose 6-phosphatase activities. It catalyzed the phosphorylation of both glucose and glucosamine with nearly the same rate and affinity. The apparent Km values for glucose and glucosamine were 0.48 ± 0.03 and 0.47 ± 0.09 mM, respectively. The catalytic efficiency (kcat/Km) values against these two substrates were 6.2 × 105 ± 0.25 and 5.8 × 105 ± 0.75 M−1 s−1. The apparent Km value for dephosphorylation of glucose 6-phosphate was ~14-fold higher than that of glucose phosphorylation. Similarly, catalytic efficiency (kcat/Km) for phosphatase reaction was ~19-fold lower than that for the kinase reaction. To the best of our knowledge, this is the first report that describes the reversible nature of a euryarchaeal ADP-dependent glucokinase.

Bioactive compounds of African star apple (Chrysophyllum albidum G. Don) and its modulatory effect on metabolic activities linked to type 2 diabetes in isolated rat psoas muscle.

The infusion of Chrysophyllum albidum was investigated for its antidiabetic mechanism by studying its ability to promote glucose uptake and utilization as well as its modulatory effect on metabolic activities linked to type 2 diabetes in isolated psoas muscle. Isolated psoas muscle was incubated with different concentrations of the infusion in the presence of glucose at 37°C for 2hr. The infusion improved muscle glucose uptake, with concomitant elevated muscular levels of glutathione, superoxide dismutase, catalase, and ectonucleotidase activities, while depleting malondialdehyde, nitric oxide, adenosine triphosphatase, acetylcholinesterase, glycogen phosphorylase, glucose 6-phosphatase, fructose-1,6-biphosphatase, and lipase activities. It also maintained muscular morphology, while increasing magnesium, calcium, and iron levels. The infusion inhibited α-glucosidase and α-amylase activities in vitro. LC-MS analysis of the infusion revealed the presence of phenolics. These results indicate that C. albidum may mediate antidiabetic activities by stimulating muscle glucose uptake and modulation of key metabolisms linked to diabetes. PRACTICAL APPLICATIONS: The African star apple is among the underutilized fruits consumed for nutritional and medicinal purposes in Western Africa. The fruits are usually wasted during its season leading to postharvest loss owing to poor utilization. The present study gives credence to its use in treating diabetes and its complications. Thus, the fruits can be utilized in the development of cheap and affordable nutraceuticals for the management of diabetes which has been reported for its high-cost treatment. Utilization of the fruits will also reduce its postharvest loss and improve its economic values.

Caffeic Acid Protects against Iron-Induced Cardiotoxicity by Suppressing Angiotensin-Converting Enzyme Activity and Modulating Lipid Spectrum, Gluconeogenesis and Nucleotide Hydrolyzing Enzyme Activities.

The protective effectsof caffeic acid on angiotensin-converting enzyme (ACE) and purinergic enzyme activities, as well as gluconeogenesis was investigated in iron-induced cardiotoxicity. Cardiotoxicity was induced in heart tissues harvested from healthy male SD rats by 0.1mM FeSO4. Treatment was carried out by co-incubating hearts tissues with caffeic acid and 0.1mM FeSO4. Cardiotoxicity induction significantly (p < 0.05) depleted GSH level, SOD, catalase, and ENTPDase activities, with concomitant elevation of the levels of malondialdehyde (MDA), nitric oxide, ACE, ATPase, glycogen phosphorylase, glucose 6-phosphatase, fructose 6-biphsophatase, and lipase activities. There was significant (p < 0.05) reversion in these levels and activities on treatment with caffeic acid. Caffeic acid also caused depletion in cardiac levels of cholesterol, triglyceride, LDL-c, while elevating HDL-c level. Our results suggest the protective effect of caffeic acid against iron-mediated cardiotoxicity as indicated by its ability to suppress oxidative imbalance and ACE activity, while concomitantly modulating nucleotide hydrolysis and metabolic switch.

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway.

Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatment. Additionally, this study also showed that the metabonomics method is a promising tool to unravel how traditional Chinese medicines work.

Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice

Obesity-associated insulin resistance (IR) is a major risk factor for developing type 2 diabetes and an array of other metabolic disorders. In particular, hepatic IR contributes to the increase in hepatic glucose production and consequently the development of fasting hyperglycemia. In this study, we explored whether kaempferol, a flavonoid isolated from Gink go biloba, is able to regulate hepatic gluconeogenesis and blood glucose homeostasis in high-fat diet-fed obese mice and further explored the underlying mechanism by which it elicits such effects. Oral administration of kaempferol (50 mg/kg/day), which is the human equivalent dose of 240 mg/day for an average 60 kg human, significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole-body insulin sensitivity without altering body weight gain, food consumption or adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase (PC) and glucose-6 phosphatase activity in the liver without altering their protein expression. Consistently, kaempferol decreased PC activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Furthermore, we found that kaempferol is a direct inhibitor of PC. These findings suggest that kaempferol may be a naturally occurring antidiabetic compound that acts by suppressing glucose production and improving insulin sensitivity. Kaempferol suppression of hepatic gluconeogenesis is due to its direct inhibitory action on the enzymatic activity of PC.

Study of Glucose-6 Phosphatase activity in Clarias batrachus (Linn.) after feeding the probiotic fish feed

Glucose-6 Phosphatase activity was studied in the air breathing fresh water catfish (Clarias batrachus) by giving the probiotic feed. The experiment was conducted in laboratory condition with glass jar aquarium. Bacteriological and different biochemical tests like cytochrome oxidase, fermentative and catalase test were analysed along with certain physiological parameters of water samples. Clarias batrachus was fed by prepared four diets, F1, F2, F3 and F4. The diets were prepared using fishmeal, soyabean meal, groundnut oil cake, rice bran, vitamin mineral mixture and different concentration of probiotics. The Clarias batrachus in experimental treatments were fed by the prepared diets upto six weeks. The significant amount of Lactic acid bacteria (LAB) was found in the gut microflora of the experimental fish. Glucose 6- phophatase activity was decreased in liver with increase in probiotic concentration in feed. But the enzyme activity in kidney, gill and stomach did not follow any trend. The water quality parameters like pH, CO2, DO, alkalinity, ammonia concentrations of the experimental tanks were varied significantly with treatment time.

Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

Studies have reported that erythritol, a lowor non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

Sapium ellipticum (Hochst) Pax ethanol leaf extract modulates glucokinase and glucose-6–phosphatase activities in streptozotocin induced diabetic rats

Abstract Objective To examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. Methods STZ-induced diabetic Wistar rats (four groups, n = 8) were used in this study. SE was assessed at two different doses, 400 and 800 mg/kg BW, in comparison with metformin (METF) (12 mg/kg BW) as a reference antidiabetic drug. All treatments were done orally (p.o), twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols. Hepatic and muscle glycogen contents were estimated as well. Results STZ caused significant decrease in glucose-6-phosphatase activity and concomitant increase in glucokinase activity. SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals. However, the effects were significantly lower than that of METF which enhanced glucokinase activity by 94.76% and simultaneously inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. Conclusions The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential.