Hepatic Glycogen Levels Research Articles

Interação do cálcio e nitrito na água: sobrevivência, crescimento, parí­¢metros hematológicos e metabólicos em jundiá

O objetivo deste estudo foi determinar o efeito de diferentes ní­­veis de nitrito (NO2-) e cálcio (Ca2+) no crescimento, parí­¢metros bioquí­­micos e hematológicos de juvenis de jundiá (Rhamdia quelen). Os peixes foram submetidos a ní­­veis baixos (0,05 mg L-1) ou elevados (1,3 mg L-1) de NO2 e baixos (7 mgL-1) ou elevados (14 mg L-1) de Ca2+ (quatro repetições) por 60 dias. No final do perí­­odo experimental, peixes expostos a alto NO2- apresentaram ganho de peso, biomassa e taxa de crescimento especí­­fico menores do que aqueles mantidos em baixos ní­­veis de NO2, independentemente dos ní­­veis de Ca2+. Peixes expostos a alto NO2/baixo Ca2+ apresentaram ní­­veis de lactato mais elevados no músculo do que peixes do grupo controle, mas um aumento dos ní­­veis de Ca2+ na água evitou este aumento. Peixes mantidos em alto NO2/alto Ca2+ mostraram ní­­veis de lactato mais elevados no fí­­gado do que aqueles expostos a baixo NO2/alto Ca2+. A exposição a ní­­veis altos de NO2 ou Ca2+ reduziu os ní­­veis de glicogênio, proteí­­na e glicose hepáticos. Peixes mantidos em alto NO2/alto Ca2+ apresentaram diminuição dos ní­­veis de hemoglobina em comparação com aqueles mantidos em baixo NO2/alto Ca2+. Portanto, a utilização de 14 mg L-1 de Ca2+ na água não minimizou a toxicidade de nitrito para R. quelen.

Preparation of the Auricularia auricular polysaccharides simulated hydrolysates and their hypoglycaemic effect

The anti-diabetic effect of the Auricularia auricular polysaccharides simulated hydrolysates (APSHs) obtained from the dried fruiting body of Auricularia auricular was studied in this paper. The APSHs were administered intragastrically (i.g.) at the dose of 0.15g/kg b.w. to the streptozotocin (STZ) –induced diabetic male SD rats for 7 weeks. The results showed that fasting blood glucose level was significantly reduced (p<0.05), whereas the glucose tolerance was remarkable improvement in STZ-induced diabetic rats through APSHs administration, and loss in body weight was also prevented in diabetic mice (p<0.05). Moreover, APSHs could increase hepatic glycogen and pancreatic insulin level (p<0.01), as well as decrease the levels of serum TG and LDL-C compared to the diabetic control group (p<0.05). APSHs had no significant effects on the total cholesterol and HDL-C levels. APSHs were composed of arabinose, xylose, mannose, glucose, galactose and glucosamine with the molar ratio of 1.91:0.52:2.89:1.00:0.67:0.23. These studies suggest that APSHs exerts marked antidiabetic effect in experimental diabetes mellitus, thus justifying the potential treatment for diabetic mellitus.

Baicalein improves insulin resistance via regulating SOCS3 and enhances the effect of acarbose on diabetes prevention

Baicalein, a major component in Scutellaria baicalensis and Oroxylum indicum, is used as dietary supplement in Asia. In this study, we characterized the insulin-sensitizing activity of baicalein and found that baicalein improved insulin resistance by reducing the expression of SOCS3, increasing the phosphorylation of IRS1 and Akt1, reducing the phosphorylation of GSK3β and increasing hepatic glycogen level. We further evaluated the preventive effect of baicalein combined with acarbose in mice, aiming to enhance the therapeutic effect and reduce the side-effects of acarbose. The combination reduced the relative risk of progression from prediabetes to diabetes by 83.3% and the dose of acarbose by 80%. The underlying mechanisms include reducing postprandial hyperglycemia, improving insulin resistance, improving lipid metabolism, and reducing oxidative stress. Our results suggest that the consumption of 195–780mg/d baicalein might improve the efficacy of acarbose on diabetes prevention and reduce the side-effects of acarbose in long-term acarbose users.

Hibiscus noldea (Malvaceae) Aqueous Extract Prevents Insulin Resistance and Protects Pancreatic Islets From Dexamethasone Damages in Rat.

&lt;p&gt;&lt;em&gt;Hibiscus noldea&lt;/em&gt; leaves-stems aqueous extract is used in Cameroonian traditional medecine to manage diabetes. To investigate the preventive effect of &lt;em&gt;Hibiscus noldea&lt;/em&gt; aqueous extract on dexamethasone-induced insulin resistance, the animals received one of the following treatments: distilled water (10 mL/kg), metformine (200 mg/kg), or &lt;em&gt;H. noldea&lt;/em&gt; (100 or 200 mg/kg) concomitantly with dexamethasone (0.5 mg/kg, ip) for ten days. Body weight was evaluated daily and blood glucose levels were measured. At the end of experiment, insulin sensitivity test was performed and lipid profile, transaminases Aspartate amino transferase, Alanin amino transferase, malondialdehyde, superoxide dismutase, catalase, and reduced glutathione were evaluated. Histological analysis of the liver was investigated to estimate glycogen content using Periodic Acid Schiff coloration and histomorphometry of pancreatic islets area was performed.&lt;/p&gt;&lt;p&gt;The administration of dexamethasone during ten days induced body weight loss, hyperglycaemia, insulinresistance, an imbalance in lipid profile, an increase in transaminases and oxidative stress. Dexamethasone treatment also induced an increase in the pancreatic islets area and depletion in the levels of hepatic glycogen. Concomitant administration of dexamethasone and the aqueous plant extract prevented the rise in blood glucose levels, reduced insulinresistance, improved lipid profile and oxidative status. The aqueous extract of &lt;em&gt;H. noldea&lt;/em&gt; prevented the use of glycogen storage and the increase in pancreatic islet area in dose dependent manner.&lt;/p&gt;&lt;p&gt;Conclusion: The stem leaves aqueous extract from &lt;em&gt;Hibiscus noldea&lt;/em&gt; have the ability to reduce insulinresistance via its antihyperglycaemic, hypolipidemic and antioxidant activities. These results justify the use of this extract in the management of diabetic state.&lt;/p&gt;

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress.

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

ObjectiveTo 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. MethodsSTZ-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. ResultsSTZ 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. ConclusionsThe 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.

Temperature during the last week of incubation. III. Effects on chicken embryo physiology

We investigated effects of eggshell temperature (EST) of 35.6, 36.7, 37.8, or 38.9°C applied from d of incubation (E) 15, E17, or E19 onward on chicken embryo physiology. A total of 2,850 first-grade eggs of a 43-week-old Ross 308 broiler breeder flock were incubated at an EST of 37.8°C until E15. From E15, E17, or E19 onward, eggs were incubated at an EST of 35.6, 36.7, 37.8, or 38.9°C. Plasma glucose, uric acid, and lactate concentrations, and hepatic glycogen amount and concentration were measured at E15, E17, E19, internal pipping (IP), external pipping (EP), and hatch.An EST of 38.9°C applied from E15 onward decreased the amount of hepatic glycogen from E19 to IP and resulted in a lower glycogen amount at IP compared to all other EST. At EP, when oxygen (O2) becomes largely available, an EST of 38.9°C resulted in a higher glycogen amount and concentration compared to IP, which suggests that plasma glucose between IP and EP might be used for building up hepatic glycogen reserves. However, hepatic glycogen levels remained considerably lower at IP, EP, and hatch at an EST of 38.9°C, compared to an EST of 35.6 and 36.7°C.Opposite to an EST of 38.9°C, from IP onward, an EST of 35.6°C resulted in a higher glycogen amount and concentration compared to all other EST, which might be caused by the higher O2 availability relative to the lower metabolic rate, which provided time to build up glycogen stores from excessive glucose. A higher availability of hepatic glycogen might contribute to an improved physiological status of the broiler chicken embryo toward hatch. Hepatic gluconeogenesis is crucial for developing embryos, as glucose is the major energy source from IP until hatch. At hatch, no effect of EST was found for glucose, uric acid, or lactate.Results of this study emphasize that EST of 35.6 and 36.7°C from E15 onward appear to be beneficial for chicken embryo physiology.

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.

Extraction and purification of pumpkin polysaccharides and their hypoglycemic effect

The anti-diabetic activity of the polysaccharides (PPs) obtained from the dried pumpkin pulp was studied in this paper. The PPs were administered by intraperitoneal injection to the alloxan-induced diabetic male ICR mice. The PPs hypoglycemic effect was evaluated by testing the fast blood glucose level, fasting serum insulin and hepatic glycogen. After 7h administration, the PPs showed a significantly hypoglycemic effect (p<0.01) and could significantly increase hepatic glycogen and insulin level (p<0.05). PPs-e with potential to enhance the islet cells proliferation activity by MTT assays in vitro was obtained from the PPs through alcohol fractional precipitation and gel chromatography. PPs-e composed of rhamnose, arabinose, glucose, galactose, and little amount of inositol could maintain the blood glucose at a low level in diabetic mice and could even last for more than 24h. These results suggest the potential hypoglycemic effect of the pumpkin polysaccharides in alloxan-induced diabetic mice and for the treatment of diabetic mellitus.

Beneficial effects of fermented sardinelle protein hydrolysates on hypercaloric diet induced hyperglycemia, oxidative stress and deterioration of kidney function in wistar rats.

This study investigated the potential effects of fermented sardinelle protein hydrolysates (FSPHs) obtained by two proteolytic bacteria, Bacillus subtilis A26 (FSPH-A26) and Bacillus amyloliquefaciens An6 (FSPH-An6), on hypercaloric diet (HCD) induced hyperglycemia and oxidative stress in rats. Effects of FSPHs on blood glucose level, glucose tolerance, α-amylase activity and hepatic glycogen content were investigated, as well as their effect on the oxidative stress state. Biochemical findings revealed that, while undigested sardinelle proteins did not exhibit hypoglycemic activity, oral administration of FSPHs to HCD-fed rats reduced significantly α-amylase activity as well as glycemia and hepatic glycogen levels. Further, the treatment with FSPHs improved the redox status by decreasing the levels of lipid peroxidation products and increasing the activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) and the level of glutathione in the liver and kidneys, as compared to those of HCD-fed rats. FSPHs were also found to exert significant protective effects on liver and kidney functions, evidenced by a marked decrease in alkaline phosphatase activity and a modulation of creatinine and uric acid contents. These results indicated the beneficial effect of FSPHs on the prevention from hyperglycemia and oxidative stress.

Anti-fatigue effects of dietary nucleotides in mice

ABSTRACTAs the building blocks of nucleic acids, nucleotides are conditionally essential nutrients that exhibit multifaceted activities. The present study aimed to evaluate the anti-fatigue effects of dietary nucleotides (NTs) on mice and explore the possible underlying mechanism. Mice were randomly divided into four experimental sets to detect different indicators. Each set of mice was then divided into four groups: (i) one control group and (ii) three NTs groups, which were fed diets supplemented with NTs at concentrations of 0%, 0.04%, 0.16%, and 0.64% (wt/wt). NTs could significantly increase the forced swimming time, enhance lactate dehydrogenase activity and hepatic glycogen levels, as well as delay the accumulation of blood urea nitrogen and blood lactic acid in mice after 30 days of treatment. NTs also markedly improved fatigue-induced alterations in oxidative stress biomarkers and antioxidant enzymes. Notably, NTs increased the mitochondrial energy metabolic enzyme activities in the skeletal muscles of mice. These results suggest that NTs exert anti-fatigue effects, which may be attributed to the inhibition of oxidative stress and the improvement of mitochondrial function in skeletal muscles. NTs could be used as a novel natural agent for relieving exercise fatigue.Abbreviations: ATP: adenosine triphosphate; BLA: blood lactic acid; GSH-Px: glutathione peroxidase; LDH: lactate dehydrogenase; MDA: malondialdehyde; NTs: dietary nucleotides; SDH: succinate dehydrogenase; SOD: superoxide dismutase; BUN: blood urea nitrogen

Protective effects of Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells in type 2 diabetic rats

Context: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes.Objective: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells protective effects in type 2 diabetes.Material and methods: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). The ethyl acetate extract (250 and 500 mg/kg) of F. carica leaves was administered for 28 days. Oral glucose tolerance (OGTT) and intraperitoneal insulin tolerance tests (ITT) were evaluated on 15th and 25th days, respectively.Results: The ethyl acetate extract (250 and 500 mg/kg) of n F. carica leaves showed significant effect (p < 0.005) in the levels of blood glucose, total cholesterol (TC), triglycerides (TG), body weight and hepatic glycogen. In OGTT, F. carica (250 and 500 mg/kg) significantly (p < 0.005) detained the increase in blood glucose levels at 60 and 120 min and in ITT, F. carica enhanced the glucose utilization significantly (p < 0.005) over 30 and 60 min compared to diabetic control. Further, the altered activities of key carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase in the liver tissue of diabetic rats were significantly (p < 0.005) reverted to near normal levels upon treatment with F. carica. Immumohistochemical studies of islets substantiated the cytoprotective effect on pancreatic β-cells.Discussion and conclusions: F. carica leaves exerted significant effect on carbohydrate metabolism enzymes with promising hypoglycemic and hypolipidemic activities in type 2 diabetic rats.

Compound 48/80, a mast cell degranulator, causes oxidative damage by enhancing vitamin C synthesis via reduced glutathione depletion and lipid peroxidation through neutrophil infiltration in rat livers.

In this study, we examined whether compound 48/80 (C48/80), a mast cell degranulator, causes hepatic oxidative damage in rats. Serum and liver biochemical parameters were determined 0.5, 3 or 6 h after a single treatment with C48/80 (0.75 mg/kg). Serum histamine and serotonin levels increased 0.5 h after C48/80 treatment but diminished thereafter. Increases in serum vitamin C (VC) and transaminases and hepatic hydrogen peroxide, lipid peroxide, and myeloperoxidase levels and a decrease in hepatic reduced glutathione level occurred 0.5 h after C48/80 treatment and further proceeded at 3 h, but these changes diminished at 6 h. Serum lipid peroxide and hepatic VC levels increased 3 h after C48/80 treatment. Hepatic glycogen level decreased 0.5 h after C48/80 treatment and further decreased at 3 h. Pre-administered ketotifen diminished all these changes found at 3 h after treatment, while pre-administered NPC 14686 diminished these changes except changes in serum histamine and serotonin levels. Hepatocellular apoptosis observed at 3 h after C48/80 treatment was attenuated by pre-administered ketotifen and NPC 14686. These results indicate that C48/80 causes oxidative damage by enhancing VC synthesis via reduced glutathione depletion-dependent glycogenolysis and lipid peroxidation through neutrophil infiltration following mast cell degranulation in rat livers.

Anti-Fatigue Effects of Small Molecule Oligopeptides Isolated from Panax ginseng C. A. Meyer in Mice.

Panax ginseng C. A. Meyer (ginseng) is an edible and medicinal Chinese herb, which is often used in Asian countries for physical fitness. Ginseng is reported to have a wide range of biological activity and pharmaceutical properties. There were more studies on ginsenosides and polysaccharides, but fewer studies on ginseng oligopeptides (GOP), which are small molecule oligopeptides isolated from ginseng. The present study was designed to evaluate the anti-fatigue effects of GOP in mice and explore the possible underlying mechanism. Mice were randomly divided into four experimental sets for the detection of different indicators. Each set of mice were then divided into four groups. The control group was administered distilled water, and three GOP intervention groups were administered 125, 250, and 500 mg/kg of body weight, respectively, of GOP by gavage each day. After 30 days of GOP treatment, it was observed that GOP could significantly increase the forced swimming time, enhance lactate dehydrogenase (LDH) activity and hepatic glycogen levels, and retard the accumulation of serum urea nitrogen (SUN) and blood lactic acid (BLA) in mice. GOP also markedly ameliorated fatigue-induced alterations of inoxidative stress biomarkers and antioxidant enzymes. Notably, GOP increased the mRNA expression of mitochondrial biogenesis factors and mitochondrial DNA content in skeletal muscles of mice. These results suggest that GOP possess anti-fatigue effects, which may be attributed to the inhibition of oxidative stress and the improvement of mitochondrial function in skeletal muscles. GOP could be a novel natural agent for relieving exercise fatigue.

Lignans-rich extract from Herpetospermum caudigerum alleviate physical fatigue in mice.

To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum (chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione (HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid (BLA), blood urea nitrogen (BUN), malondialdehyde (MDA), hepatic glycogen (HG), lactic dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) determined following the recommended procedures provided by the commercial kits. Compared with the control group, the lignans extract (ethyl acetate fraction) of Herpetospermum caudigerum and HPE could signifificantly prolonged the exhaustive swimming time (P<0.05 or P<0.01), and also increased the HG levels (P<0.05 or P<0.01) and the activities of antioxidant enzymes (SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups (P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group (P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters. The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.

Reducing oxidative stress and hepatoprotective effect of water extracts from Pu-erh tea on rats with high-fat diet

Reducing oxidative stress and hepatoprotective effect of Pu-erh tea water extracts on rats fed with high-fat diet were researched for explaining health care of Pu-erh tea. Fifty SD rats were divided into five groups. The body weight was measured once a day. The malondialdehyde (MDA) and glucose (Glu) levels and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide synthase (NOS), and pyruvate kinase (PK) in serum were determined. Furthermore, the hepatic glycogen level (HGL) and the activities of hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were also measured after continuous administration for 12 weeks. The result demonstrated that Pu-erh extract caused the decreases in body weight, fat index, MDA and NOS levels, and the increases in hepatic T-SOD, CAT and GSH-Px activities, indicating that the extract may be due to inhibiting the increases of body weight and fat index, reducing oxidant stress state and inhibiting lipid peroxidation, thus decreasing the activities of ALT and AST, and protecting the liver in rat. Meanwhile, the extracts could increase the production of hepatic glycogen and the activity of PK, and reduce glucose level, protecting the liver from the diseases associated with type II diabetes.

Combined Deletion of Slc30a7 and Slc30a8 Unmasks a Critical Role for ZnT8 in Glucose-Stimulated Insulin Secretion.

Polymorphisms in the SLC30A8 gene, which encodes the ZnT8 zinc transporter, are associated with altered susceptibility to type 2 diabetes (T2D), and SLC30A8 haploinsufficiency is protective against the development of T2D in obese humans. SLC30A8 is predominantly expressed in pancreatic islet β-cells, but surprisingly, multiple knockout mouse studies have shown little effect of Slc30a8 deletion on glucose tolerance or glucose-stimulated insulin secretion (GSIS). Multiple other Slc30a isoforms are expressed at low levels in pancreatic islets. We hypothesized that functional compensation by the Slc30a7 isoform, which encodes ZnT7, limits the impact of Slc30a8 deletion on islet function. We therefore analyzed the effect of Slc30a7 deletion alone or in combination with Slc30a8 on in vivo glucose metabolism and GSIS in isolated islets. Deletion of Slc30a7 alone had complex effects in vivo, impairing glucose tolerance and reducing the glucose-stimulated increase in plasma insulin levels, hepatic glycogen levels, and pancreatic insulin content. Slc30a7 deletion also affected islet morphology and increased the ratio of islet α- to β-cells. However, deletion of Slc30a7 alone had no effect on GSIS in isolated islets, whereas combined deletion of Slc30a7 and Slc30a8 abolished GSIS. These data demonstrate that the function of ZnT8 in islets can be unmasked by removal of ZnT7 and imply that ZnT8 may affect T2D susceptibility through actions in other tissues where it is expressed at low levels rather than through effects on pancreatic islet function.

Formononetin exhibits anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice.

The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect on some diabetes-related indices as described below. Body weight, fasting blood glucose, hepatic glycogen, serum insulin, and serum glucagon were determined by electronic scales, glucometer, and ELISA kits. Fas, Caspase-3, pancreatic and duodenal homeobox-1 , insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase and glucose-6-phosphatase mRNA, and proteins levels in liver tissue were detected by fluorogenic quantitative-polymerase chain reaction and Western blot assays. The results indicated that formononetin (5, 10, and 20 mg/kg; oral administration) reversed the alloxan-induced increase of some indices (fasting blood glucose level and Fas and Caspase-3 mRNA and proteins levels in pancreas tissue) and reduction of some indices (body weight gain, oral glucose tolerance, insulin activity, hepatic glycogen level, pancreatic and duodenal homeobox-1, insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase mRNA and protein levels in liver tissue). The glucagon level and glucose-6-phosphatase mRNA and protein levels in liver tissue were not affected by the drugs administration. In conclusion, formononetin exhibited anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice by inhibiting islet B cell apoptosis and promoting islet B cell regeneration, insulin secretion, hepatic glycogen synthesis, and hepatic glycolysis.

Ethanolic Extract of Bauhinia forficata: Metabolic Effects in Diabetic and Normoglycemic Rats

Liver infusion of BFEE in fed and fasted diabetic rats reduced glucose and lactate production, respectively; however, BFEE did not affect glycemia or hepatic glycogen levels. Plasma transaminases increased in diabetic animals receiving the extract. The STZ model reduced by nearly half the number of Langerhans’ islets in comparison to non-diabetic animals, however no pancreatic difference was observed between diabetic animals treated with extract and diabetic animals treated with vehicle.

Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis.

Liver glycogen is important for the counterregulation of hypoglycemia and is reduced in individuals with type 1 diabetes (T1D). Here, we examined the effect of varying hepatic glycogen content on the counterregulatory response to low blood sugar in dogs. During the first 4 hours of each study, hepatic glycogen was increased by augmenting hepatic glucose uptake using hyperglycemia and a low-dose intraportal fructose infusion. After hepatic glycogen levels were increased, animals underwent a 2-hour control period with no fructose infusion followed by a 2-hour hyperinsulinemic/hypoglycemic clamp. Compared with control treatment, fructose infusion caused a large increase in liver glycogen that markedly elevated the response of epinephrine and glucagon to a given hypoglycemia and increased net hepatic glucose output (NHGO). Moreover, prior denervation of the liver abolished the improved counterregulatory responses that resulted from increased liver glycogen content. When hepatic glycogen content was lowered, glucagon and NHGO responses to insulin-induced hypoglycemia were reduced. We conclude that there is a liver-brain counterregulatory axis that is responsive to liver glycogen content. It remains to be determined whether the risk of iatrogenic hypoglycemia in T1D humans could be lessened by targeting metabolic pathway(s) associated with hepatic glycogen repletion.