Hepatic Glycogen Content Research Articles

Physiological Ecology of Winter Hibernation by the High-Altitude Frog Nanorana parkeri.

AbstractThe Xizang plateau frog, Nanorana parkeri (Anura: Dicroglossidae), enters a dormant state in the winter in response to seasonal cold and lack of food. To investigate the physiological and ecological characteristics of overwintering in this species, we measured habitat conditions (hibernacula temperatures, body temperature, and water quality variables), morphology, metabolite concentrations, total antioxidant capacity (T-AOC), and bacteria-killing ability (BKA) of plasma during summer and winter. We found that N. parkeri hibernates underwater at the bottom of ponds (10-20-cm depth). Dissolved oxygen content in the water decreases significantly (by 12%) in the winter compared with summer, suggesting that overwintering N. parkeri may experience hypoxia. Body mass, body mass index, hepatosomatic index, and hepatic glycogen concentration all increased significantly in winter-collected frogs as compared to summer-collected individuals, indicating that overwintering N. parkeri accumulates high fuel/energy reserves to support prolonged periods of hibernation. A significant reduction in glucose, urea, and lactate concentrations in most organs may be closely related to metabolic depression in overwintering N. parkeri. Liver lactate concentration rose significantly in winter-collected frogs, suggesting that anaerobic metabolism dominates when this species overwinters. The T-AOC of plasma showed a significant reduction in winter, suggesting a reduced need for antioxidant defenses. Oppositely, the BKA of plasma increased significantly in winter versus summer, indicating that innate immunity was enhanced during overwintering. In summary, these behavioral (migrating to caves), physiological, and biochemical adjustments may be key for the successful overwintering of this high-altitude frog.

Yeast culture improved the growth performance, liver function, intestinal barrier and microbiota of juvenile largemouth bass (Micropterus salmoides) fed high-starch diet

The present study was conducted to investigate the effects of yeast culture on the growth, health and microflora of the juvenile largemouth bass fed high-starch diet. The experiment set three isonitrogenous and isolipidic diets, control (high-starch diet), HSY1 (high-starch diet with 1% yeast culture) and HSY3 (high-starch diet with 3% yeast culture). A feeding trial was conducted in largemouth bass juveniles for 8 weeks. The results indicated fish fed with 3% yeast culture not only could improve specific growth rate (SGR), but also significantly decreased hepatic lipid content, hepatic glycogen content, and hepatopancreas somatic index (HSI) compared with the control group (p<0.05). The total superoxide dismutase (T-SOD) and catalase (CAT) activities of HSY3 group significantly increased while malondialdehyde (MDA) content significantly reduced in liver compared with the control group (p<0.05). Meanwhile, the mRNA expression levels of hepatic Sod and Cat were up-regulated (p<0.05), and liver metabolism showed 111 metabolites were significantly changed in HSY3 group, liver lipid metabolism pathway remarkably changed. Besides, the intestinal anti-inflammatory cytokines were significantly up-regulated, and the pro-inflammatory cytokines were significantly down-regulated as the inclusion of yeast culture (p<0.05). Notably, HSY3 group diet up-regulated the expression of Zo-1, Claudin and Occludin in intestine compared with the other groups (p<0.05). Serum d-lactate (D-lac), diamine oxidase (DAO) and lipopolysaccharide (LPS) decreased significantly with the inclusion of yeast culture (p<0.05). Furthermore, the abundance of probiotics (such as Lactobacillus, Bacillus and Bifidobacterium) increased significantly, and the abundance of intestinal potential pathogenic bacteria (Plesiomonas) decreased in HSY3 group (p<0.05). The phenotypic analysis showed that gram-negative bacteria significantly decreased while gram-positive bacteria increased in HSY3 group (p<0.05). All in all, this study revealed that supplementation of 3% yeast culture can improve the growth performance and the health of juvenile largemouth bass, and has the potential to be used as an effective synbiotics for M. salmoides.

Pancreastatin inhibitor PSTi8 prevents free fatty acid-induced oxidative stress and insulin resistance by modulating JNK pathway: In vitro and in vivo findings

AimFree fatty acid-mediated obesity plays a crucial role in the pathogenesis of Type 2 Diabetes. FFA induced JNK activation acts as a central regulator in causing hepatic insulin resistance. Similarly, Pancreastatin, a chromogranin A peptide, serves as a crucial link between FFA-induced insulin resistance. Therefore, in the present work, we sought to test Pancreastatin inhibitor PSTi8 to ameliorate FFA-induced hepatic insulin resistance in in vitro and in vivo models. Material and methodsTo verify our objective, we exposed hepatocytes (HepG2 cells) with palmitate (0.3 mM) or palmitate + PSTi8 (200 nM). Parallelly mice were fed either HFD or HFD + PSTi8 (1 mg/kg). After 21 days animals were scanned for increased fat mass, along with GTT, ITT and PTT experiment to check glucose, and insulin tolerance. Furthermore, ROS generation and hepatic glycogen content was measured in FFA exposed hepatocytes. Gene expression and protein expression studies were further conducted to delineate the action mechanism of PSTi8. Key findingsPSTi8 exposure decreased ROS accumulation, lipid accumulation, and reduced glycogen content in FFA-induced groups. It also enhances glucose uptake and reduces gluconeogenesis to combat the FFA effect. Furthermore, gene expression studies indicate that PSTi8 treatment reduces NADPH oxidase3 (NOX3) expression and inhibits JNK signaling, a predominant source of ROS-induced insulin resistance. SignificanceTo summarize, the protective effect of PSTi8 on FFA-induced insulin resistance is mediated via inhibition of JNK signaling, which leads to decreased ROS generation and enhanced insulin sensitivity. Hence PSTi8 could be a therapeutic molecule to prevent western diet-induced insulin resistance.

Bisphenol AF exposure causes fasting hyperglycemia in zebrafish (Danio rerio) by interfering with glycometabolic networks.

Bisphenol AF (BPAF), one of the main alternatives to bisphenol A, has been frequently detected in various environmental media, including the human body, and is an emerging contaminant. Epidemiological investigations have recently shown the implications of exposure to BPAF in the incidence of diabetes mellitus in humans, indicating that BPAF may be a potential diabetogenic endocrine disruptor. However, the effects of BPAF exposure on glucose homeostasis and their underlying mechanisms in animals remain largely unknown, which may limit our understanding of the health risks of BPAF. To this end, zebrafish (Danio rerio), an emerging and valuable model in studying animal glycometabolism and diabetes, were exposed to environmentally relevant concentrations (5 and 50μg/L) and 500μg/L BPAF for 28 d. Several key toxicity endpoints of blood glucose metabolism were detected in our study, and the results showed significantly increased fasting blood glucose levels, hepatic glycogen contents and hepatosomatic indexes and decreased muscular glycogen contents in the BPAF-exposed zebrafish. The results of quantitative real-time PCR showed the abnormal expression of genes involved in glycometabolic networks, which might promote hepatic gluconeogenesis and inhibit glycogenesis and glycolysis in the muscle and/or liver. Furthermore, the failure of insulin regulation, including plasma insulin deficiency and impaired insulin signaling pathways in target tissues, may be a potential mechanism underlying BPAF-induced dysfunctional glycometabolism. In summary, our results provide novel in vivo evidence that BPAF can cause fasting hyperglycemia by interfering with glycometabolic networks, which emphasizes the potential health risks of environmental exposure to BPAF in inducing diabetes mellitus.

Short‐term metabolic responses of gilthead seabream,Sparus aurata, fed diets with different protein and protein: Energy levels

The present study aimed to evaluate, in gilthead sea bream, the effect of dietary protein:energy (P/E) ratio and non-protein energy (NPE) source on the post-prandial profile of plasmatic parameters, hepatic energy reserves, enzymatic activities of digestive enzymes and hepatic key enzymes activities of the glycolytic (HK and GK), lipogenic (G6PDH and FAS), gluconeogenic (FBPase) and amino acid (GDH, AST and ALT) metabolic pathways. Fish (44 ± 0.05 g) were fed for 34 days four diets with high (HP) or low (LP) P/E ratios and lipid (L) or starch (S) as NPE source (diets HPL, HPS, LPL and LPS, respectively). No differences in growth performance were observed between groups. However, FI was lower, and FE was higher in fish fed the HPS diet than in other groups. Plasma triglycerides and glycaemia were affected by diet composition. Hepatic glycogen and lipid content of fish fed the HPL diet were lower than other groups at different post-prandial times. Digestive enzymes peaked between 6 and 12 h after feeding. HK and GK activities peaked at 6 h after feeding and followed the amylase activity peak. Glycolysis and lipogenesis enzyme activities were higher in fish fed the starch than lipid diets. Gluconeogenesis enzyme activity was high, and amino acid catabolism enzyme activity was lower in fish fed the LP than HP diets. In conclusion, dietary NPE sources and P/E ratio affected the metabolic responses in gilthead sea bream; overall, NPE sources affected carbohydrate metabolism and lipogenesis, whereas P/E ratio mainly affected gluconeogenesis and amino acid catabolism.

Adverse effects of perinatal protein restriction on glucose homeostasis in offspring of Sprague-Dawley rats

Adequate evidence suggests that poor in-utero environment produced by early life dietary disturbance may predispose offspring to chronic diseases in adult life. It remains to be defined the adverse effect of early exposure due to perinatal protein restriction (PPR) (gestation, lactation and/or both) on the regulators of glucose homeostasis of the male offspring in later life. Hence, the present study investigated the role of perinatal protein restriction on the regulators of glucose homeostasis in adult offspring. Twenty-four pregnant and twelve male Sprague-Dawley rats were used. They were fed either a normal diet containing 20% protein or protein-restricted (PR) diet with 8% protein. The dams were given PR diet up to parturition (in-utero group, IUPR), or from birth to postnatal day 21 (lactation group, LPR) or for a period covering both groups (combined group, CPR). Control dams with control diet was run in parallel for comparison. At day 120, oral glucose tolerance, insulin tolerance, fasting blood glucose, fasting insulin level were determined. Hepatic and myocytic glycogen contents, GLUT-4 protein abundance, alpha amylase and alpha glucosidase activities were also assessed. The results revealed that glucose tolerance was unchanged, insulin sensitivity was significantly decreased in IUPR and CPR offspring. HOMA-IR elicited a significant elevation (p<0.01) in IUPR and CPR offspring compared with CONT. Hepatic and myocytic glycogen contents in all PPR offspring significantly decreased compared with CONT. GLUT-4 protein was significantly (p<0.01) reduced in all PPR offspring compared with CONT. Alpha amylase activity decreased significantly (p<0.01) in IUPR and CPR offspring with a significant increase (p<0.01) in LPR offspring compared with CONT. However, alpha glucosidase activity showed no significant difference (p>0.01) in all PPR offspring compared with CONT. In conclusion, the data described in the present investigation provides ample evidence that PPR remarkably malprogram the offspring to impairment of glucose homeostasis with blunted insulin action in the tissues of the periphery which eventually reduces uptake of glucose, utilization and absorption as well as deposition of glycogen in liver and skeletal muscle leading to insulin resistance in PPR offspring.

IMPACT OF INDUSTRIAL POLLUTANTS ON CARBOHYDRATE METABOLISM IN CHANNA PUNCTATUS (BLOCH)

The freshwater air-breathing fish Channa punctatus was exposed to sub-lethal concentration of mercuric chloride, cadmium chloride, phenol, ammonia and mixture of these four for 48 hours to determine the short-term effects of these industrial pollutants on carbohydrate metabolism. Fishes were found to be hyperglycemic with a concomitant depletion in the hepatic glycogen content and increase in glucose-6-phosphatase activity on 1st and 2nd day of exposure to single and mixture of pollutants. The results clearly indicate that hepatic glycogen is a major source of hyperglycemia in C. punctatus. Both gluconeogenesis and glycogenolysis result in the formation of glucose-6-phosphate, which is hydrolyzed by glucose-6-phosphatase, found in liver and kidney, before being liberated as glucose into the circulation. Histopthological changes in the hepatopancreas of C. punctatus induced by the pollutants include degeneration of hepatocytes accompanied by karyolysis, apoptosis and necrosis, clumping of cytoplasmic materials, derangement of the pancreatic acini and coagulation of blood in the sinusoids. Renal kidney exhibited tubular degeneration and changes in the corpuscles such as shrinkage of capillaries in the glomeruli and increase in Bowman’s space. It is inferred that industrial pollutants effects the normal hepatic and renal functions of C. punctatus. Key words: Channa punctatus, industrial-pollutants, hepatic glycogen, glucose-6-phosphatase, glomeruli, Bowman’s space

PSII-17 The differential expression pattern of messenger RNA for key hepatic glycogen metabolizing proteins is consistent with hepatic glycogen content in suckling pigs

Abstract The effect of developmental age (d) on expression of genes responsible for hepatic glycogen (GLY) synthesis and degradation, glucose flux, and GLY content, was determined in crossbred pigs euthanized (n = 6) at birth (d 0, pre-suckle), 1, 3, 7, 14, and 21 d. Liver GLY content and relative abundance of mRNA (RT-PCR) was determined. The relative content of liver mRNA was determined in 2 experiments, d 0, 1, 3, 7 (Experiment 1) and d 0, 1, 7, 14, 21 (Experiment 2). Within each experiment, data were analyzed using the GLM procedure of SAS. Fisher’s protected LSD procedure was used to separate treatment means. Day 0 (76.0) GLY content (mg/g) decreased (P &amp;lt; 0.01) 82% from d 0 to d 1, increased (P &amp;lt; 0.05) from d 1 (13.8) through d 14 (28.4), and did not differ (P = 0.07) between d 1 and 21. In Experiment 1, mRNA content of GLY synthesis proteins GYG1 and GYS1 was greatest (P &amp;lt; 0.01) at d 3 and 7; and 1 and 3; respectively, whereas mRNA content of GLY degrading proteins PGM1, PGM2, and PGM5 was greatest (P ≤ 0.01) at d 1; d 0; and d 1 and 7; respectively. In Experiment 2, mRNA content of GLY synthesis proteins GBE1 and GYS1 was greatest (P &amp;lt; 0.01) at d 0 and 21; and d 1 and 21; respectively, whereas mRNA content of GLY degrading proteins AGL, PGM2, PGM2L, and PGM5 was greatest (P &amp;lt; 0.01) at d 21; d 0; d 7, 14, and 21; and d 14 and 21; respectively. Glucose transporter SGLT1 mRNA content was greatest (P &amp;lt; 0.01) at d 14 and 21. These findings indicate that the pattern of mRNA content of key hepatic GLY degradation and synthesis proteins was consistent with GLY content of suckling pigs.

Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats

AimsGlucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism. Materials and methodsAdult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses. Key findingsDexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances. SignificanceCoadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats.

TRPV1 Receptor-Mediated Hypoglycemic Mechanism of Capsaicin in Streptozotocin-Induced Diabetic Rats.

Our previous research showed that capsaicin exhibits hypoglycemic effects by activating the transient receptor potential vanilloid 1 (TRPV1) channel in diabetic rats. Interestingly, capsiate was also able to activate the TRPV1 channel, but with a non-significant hypoglycemic effect. This study aimed to investigate the effect of capsaicin on the glycometabolism of streptozotocin (STZ)-induced diabetic rats by blocking the TRPV1 channel. After a 4-week capsaicin treatment (6 mg/kg·bw), the serum insulin level of STZ-induced diabetic rats increased from 15.2 to 22.1 mIU/L, the content of hepatic glycogen and muscle glycogen increased by 81.2 and 20.2%, respectively, and the blood glucose level decreased significantly from 19.3 to 14.7 mmol/L. When the TRPV1 channel was blocked, capsaicin lost the above-mentioned effects, and the hypoglycemic effect was no longer significant. It was concluded that a combined up-regulation of both TRPV1 receptors and pancreatic duodenal homeobox-1 (PDX-1) led to the hypoglycemic effect of capsaicin, which partially explains our previous observation: capsiate activating TRPV1 without showing a significant hypoglycemic effect was due to the lack of a significant up-regulation of PDX-1. Based on the experimental results, we speculated that two signaling pathways [TRPV1-(PDX1)-(GLUT2/GK) and TRPV1-(PDX-1)-(IRS1/2)] exist in the pancreas of STZ-induced diabetic rats.

YiQi YangYin Decoction Attenuates Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Rats.

Background YiQi YangYin Decoction (YQ) is a modern Chinese formula composed by the guidance of traditional Chinese medicine theory, which consists of nine traditional Chinese medicines and is applied to treat type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver in clinic in China for more than a decade. This study aims to evaluate the antidiabetes and lipid-lowering effect of YQ and explore the possible mechanisms of this action. Methods T2DM rat models were established and given YQ at three different doses for three weeks. Tissues, including pancreas islet and liver, and blood serum were collected. The levels of fasting blood glucose (FBG), fasting insulin (Fins), lipid index, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and hepatic function index such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum were measured. Pancreas islet damage and liver damage were observed by hematoxylin and eosin staining. The glycogen content and lipid accumulation in liver were determined by periodic acid-Schiff (PAS) staining and Oil Red O staining. The expression levels of insulin receptor substrate 2 (IRS-2), phosphatidylinositol 3 kinase-associated p85alpha (PI3K p85α), AKT, and Glucose Transporter 2 (Glut4) in pancreas islet and AMP-activated protein kinase alpha (AMPKα), sterol regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase (ACC1), and peroxisome proliferator‐activated receptor-α (PPARα) in liver were determined by western blotting. The relative expressions of ACC1, fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), carnitine palmityl transferase-1 (CPT-1), and SREBP-1 mRNA were detected by qRT-PCR. Results After administering YiQi for three weeks, the levels of fast blood glucose, fasting insulin, TC, TG, LDL, ALT, AST, and ALP were significantly decreased, while HDL significantly increased compared with the model group. YQ could obviously attenuate pancreatic damage and improve islet α- and ß-cell survival compared with the model group. Furthermore, YQ could attenuate hepatic damage caused by lipid accumulation, decrease the content of lipid, and increase the hepatic glycogen content, compared with the model group. In addition, YQ remarkably elevated the proteins expression of p-PI3K, p-AKT, and GLUT4 in pancreas islet and elevated the proteins expression of p-PI3K, p-AKT, GLUT4, p-AMPK, SREBP1, and PPARα and inhibited the expression of p-ACC1 in liver. Besides, YQ reduced the relative expression of ACC1, FAS, SERBP-1c, and SCD mRNA along with the decreased production of CPT-1 mRNA. Conclusions YQ could attenuate type 2 diabetes mellitus by improving islet α- and ß-cells via IRS-2/AKT/GLUT4 pathway and nonalcoholic fatty liver by ameliorating lipid accumulation via AMPK/PPARα/SREBP1/ACC1 pathway.

Effects of glimepiride on growth, glucose metabolism and expression of p38MAPK, JNK in skeletal muscles of GIFT tilapia

This study aimed to investigate the effects of glimepiride on the growth, glucose metabolism and the expressions of p38 mitogen-activated protein kinases (p38MAPK), C-JUN N-terminal kinase (JNK) in skeletal muscle of genetically improved farmed tilapia (GIFT). The tilapia were categorized into five feed groups: normal starch group (32%, LS), high starch group (53%, HS), HS+ glimepiride group 1 (10 mg/kg, G1), HS+ glimepiride group 2 (20 mg/kg, G2), and HS+ glimepiride group 3 (30 mg/kg, G3). The results showed that the final body weight and specific growth rate of the G2 group increased (P > 0.05), and the protein efficiency ratio of groups G1 and G2 was significantly higher than that of the HS group (P < 0.05). The blood glucose content of groups G2 and G3 decreased, compared to that of the HS group. An increase in the glimepiride concentration led to the decreased serum glucose content of the G1 and G2 groups. Compared with the HS group, the insulin content of the G1, G2, and G3 groups significantly decreased, and the hepatic and muscle glycogen content in these three groups increased gradually with an increase in the glimepiride concentration (P > 0.05). The expression of p38MAPK and JNK mRNAs in the G1 and G2 groups were significantly lower than those in the HS groups (P < 0.05). In the G2 and G3 groups, p-p38MAPK and p-JNK protein expression were significantly lower than that in the HS group (P < 0.05); meanwhile, the p-JNK protein expression in G1 and G2 groups was lower than that in the HS group (P > 0.05). Thus, GIFT tilapia can tolerate a high amount of starch, and the addition of glimepiride at an optimal dosage of 10–20 mg/kg does not significantly impact the growth index. However, it can improve glucose metabolism by promoting insulin secretion and liver/muscle glycogen synthesis.

Somatostatin Receptor Antagonism Reverses Glucagon Counterregulatory Failure in Recurrently Hypoglycemic Male Rats.

Recent antecedent hypoglycemia is a known source of defective glucose counter-regulation in diabetes; the mechanisms perpetuating the cycle of progressive α-cell failure and recurrent hypoglycemia remain unknown. Somatostatin has been shown to suppress the glucagon response to acute hypoglycemia in rodent models of type 1 diabetes. We hypothesized that somatostatin receptor 2 antagonism (SSTR2a) would restore glucagon counterregulation and delay the onset of insulin-induced hypoglycemia in recurrently hypoglycemic, nondiabetic male rats. Healthy, male, Sprague-Dawley rats (n = 39) received bolus injections of insulin (10 U/kg, 8 U/kg, 5 U/kg) on 3 consecutive days to induce hypoglycemia. On day 4, animals were then treated with SSTR2a (10 mg/kg; n = 17) or vehicle (n = 12) 1 hour prior to the induction of hypoglycemia using insulin (5 U/kg). Plasma glucagon level during hypoglycemia was ~30% lower on day 3 (150 ± 75 pg/mL; P < .01), and 68% lower on day 4 in the vehicle group (70 ± 52 pg/mL; P < .001) compared with day 1 (219 ± 99 pg/mL). On day 4, SSTR2a prolonged euglycemia by 25 ± 5 minutes (P < .05) and restored the plasma glucagon response to hypoglycemia. Hepatic glycogen content of SSTR2a-treated rats was 35% lower than vehicle controls after hypoglycemia induction on day 4 (vehicle: 20 ± 7.0 vs SSTR2a: 13 ± 4.4 µmol/g; P < .01). SSTR2a treatment reverses the cumulative glucagon deficit resulting from 3 days of antecedent hypoglycemia in healthy rats. This reversal is associated with decreased hepatic glycogen content and delayed time to hypoglycemic onset. We conclude that recurrent hypoglycemia produces glucagon counterregulatory deficiency in healthy male rats, which can be improved by SSTR2a.

Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2.

Campomanesia xanthocarpa, a plant belonging to the Myrtaceae family, is popularly known as gabiroba. Leaves of gabiroba has been popularly used to treat various diseases, including inflammatory, renal, and digestive, among others. Additionally, studies have shown an effect to reduce blood cholesterol levels. The aim of this study was to evaluate the antihyperglycemic and hypolipidemic effects of Campomanesia xanthocarpa seed extract in hyperglycemic rats. The results showed that 400 mg/kg of seed extract was able to decrease blood glucose levels and to increase the muscular and hepatic glycogen content as well as to inhibit the sucrase and maltase activity. At doses of 200 mg/kg and 800 mg/kg, the activity of these enzymes was also reduced. In the lipid profile 400 mg/kg produced a decrease in total and LDL cholesterol serum levels; and with 200 mg/kg there was an increase in HDL cholesterol levels. The extract did not present hepatic and renal toxic effects at the different doses tested. The results suggest that the treatment with Campomanesia xanthocarpa seeds extract is useful in reducing glycemia, total cholesterol and LDL levels with potential adjuvant therapeutic in the treatment of diabetes and hypercholesterolemia, however, additional pharmacological and toxicological studies are still required.

Aloe vera carbohydrates regulate glucose metabolism through improved glycogen synthesis and downregulation of hepatic gluconeogenesis in diabetic rats

Ethnopharmacological relevanceAloe vera (L.) Burm.f. is an ancient medicinal plant that belongs to the family Asphodelaceae. It has a rich source of bioactive constituents such as carbohydrates, polyphenols, peptides, sterols and tannins, etc. Aloe vera has multiple biological activities such as anti-inflammatory, antioxidant and antidiabetic activity etc. Aim of the studyThe present study investigated the antidiabetic mechanism of Aloe vera carbohydrate fraction (AVCF) and aimed to provide insights into the regulation of carbohydrate metabolism enzymes in glucose homeostasis. Materials and methodsThe antidiabetic effect of AVCF was evaluated using α-amylase, α-glucosidase inhibition, glucose diffusion and glucose uptake assay. The in vitro AVCF effect on insulin secretion, cell proliferation and inflammatory markers were determined using streptozotocin-induced oxidative stress on RIN-m5F cells. Streptozotocin-induced male Wistar diabetic rats were treated for 21 days with AVCF (54 mg/kg bw). The in vivo AVCF effect was measured on fasting plasma glucose, insulin, glucagon, hexokinase, glycogen synthase and glucose-6-phosphatase, levels in diabetic rats. Histopathological studies for organ-specific effects in the pancreas, liver and small intestine were also conducted. ResultsAVCF-treated RIN-m5F cells significantly increased BrdU levels, with insulin secretion, and decreased TNF-α, IL-6 and nitric oxide levels. AVCF treated streptozotocin-induced diabetic rats showed significantly decreased fasting plasma glucose, glucagon and glucose-6-phosphatase levels with a concomitant increase in insulin, hexokinase, and glycogen synthase levels and, glycogen content. These findings corroborate with the improved hepatic glycogen content in the PAS stained histological section of the liver of AVCF treated diabetic rats. ConclusionThese results suggest that CF of Aloe vera improved glucose metabolism by activation of glycogenesis and down-regulation of gluconeogenesis thereby, maintaining glucose homeostasis. Hence, AVCF can be used as an alternative medicine in the alleviation of diabetes mellitus symptoms.

30-Day spexin treatment of mice with diet-induced obesity (DIO) and type 2 diabetes (T2DM) increases insulin sensitivity, improves liver functions and metabolic status

Spexin (SPX) is a 14 aa peptide discovered in 2007 using bioinformatics methods. SPX inhibits food intake and regulates lipid, and carbohydrate metabolism. Here, we evaluate the ability of SPX at improving metabolic control and liver function in obese and type 2 diabetic animals. The effects of 30 days SPX treatment of mice with experimentally induced obesity (DIO) or type 2 diabetes (T2DM) on serum glucose and lipid levels, insulin sensitivity and hormonal profile (insulin, glucagon, adiponectin, leptin, TNF alpha, IL-6 and IL-1β) are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. We report that SPX decreases body weight in healthy and DIO mice, and reduces lipid content in all three animal groups. SPX improves insulin sensitivity in DIO and T2DM animals. In addition, SPX modulates hormonal and metabolic profile by regulating the concentration of adiponectin (concentration increase) and leptin (concentration decrease) in the serum blood of DIO and T2DM mice. Lastly, SPX decreases lipid content as well as IL-6 and TNF-α protein levels in liver of DIO and T2DM mice, and reduces IL-6 and TNF-alpha concentrations in the serum derived from T2DM mice. Based on our results, we conclude that SPX could be involved in the development of obesity and type 2 diabetes mellitus and it can be further evaluated as a potential target for therapy of DIO and T2DM.

Metabolic responses of Chinese perch (Siniperca chuatsi) to different levels of dietary carbohydrate.

There are great differences in metabolic responses to different levels of carbohydrate among different carnivorous fish species. To explore metabolic responses of Chinese perch to moderate and high level of dietary carbohydrates, three diets containing 7.3% (LC), 17.5% (MC), and 27.5% (HC) of carbohydrates were provided to Chinese perch for 56days. The results showed that MC and HC groups exhibited an increase in weight gain (WG) and hepatic glycogen content, and a decrease in feed conversion efficiency, compared with the LC group. The MC and HC groups also showed the increase in mRNA levels of phosphofructokinase and citrate synthase related to the aerobic oxidation pathway, which might be responsible for the increase in WG. Moreover, compared with the LC group, the HC group exhibited high levels of plasma indices (glucose, pyruvic acid, lactic acid, total triglyceride, total cholesterol, and low-density lipoprotein) and liver lipid resulting from the increased mRNA levels of fatty acid synthesis-related genes (ATP citrate lyase, acetyl-CoA carboxylase α, and fatty acid synthase), low level of crude protein caused by inhibition of TOR pathway, and liver damage induced by low antioxidant capacity and infiltration of inflammatory cells, but the MC group did not. The above results indicated that 17.5% dietary carbohydrate might be utilized effectively in Chinese perch and part carbohydrates were converted into glycogen to maintain glucose homeostasis; 27.5% dietary carbohydrate could not be fully utilized. The 27.5% carbohydrate diet induced the up-regulation of aerobic oxidation, glycogen synthesis, and fat synthesis pathways which might not be sufficient to maintain glucose homeostasis.

Acanthopanax senticosus Promotes Survival of Tilapia Infected With Streptococcus iniae by Regulating the PI3K/AKT and Fatty Acid Metabolism Signaling Pathway.

Streptococcus has greatly restricted the development of healthy tilapia aquaculture. As a green and efficient feed addition, Acanthopanax senticosus (APS) has been increasingly used in culture, but it is unclear whether it represents a disease-resistant feed. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus) was fed with a feed supplemented with 0 (control), 0.5, 1, 2, 4, and 8‰ APS for 56 days, after which fish were injected with 5.9 × 106 CFU/ml Streptococcus iniae into the abdominal cavity. At 96 h after infection, the cumulative survival of GIFT in control and 0.5‰ APS treatments was significantly lower than in other treatments; at APS supplementation rates of 1 and 2‰, serum glucose, triglycerides, and cholesterol contents were all significantly lower than in control treatment fish. Hepatic glycogen and triglyceride contents of 1‰ APS treatment fish were significantly higher than those in fish in control treatment. Transcription levels of peroxisome proliferator activated receptor α (PPAR), fatty acid synthase (FAS), and lipoprotein Lipase (LPL) genes were upregulated, and their expression levels in fish in 1, 2, and 4‰ treatments were significantly higher than those in fish in control treatment at 96 h after S. iniae infection. After 96 h of infection, the red blood cells, hemoglobin, hematocrit, and white blood cells of fish in 1‰ APS treatment were significantly lower than those of fish in 4 and 8‰ treatments; hepatic catalase activity was activated at 48 h, superoxide dismutase activity was also significantly upregulated at 96 h, and the malondialdehyde content significantly decreased. It is noted that 0.5–2‰ APS treatments significantly activated the expression of PI3K and AKT in the liver, while inhibiting the expression of Caspase-9. Therefore, feed with 1‰ APS can promote hepatic glycogen and lipid metabolism in GIFT after infection with S. iniae, which is beneficial to alleviating oxidative stress damage and cell apoptosis in liver tissue.

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model.

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.

Hepatic fatty acids profile, oxidative stability and egg quality traits ameliorated by supplementation of alternative lipid sources and milk thistle meal.

This study assessed the effects of different levels of milk thistle (Silybum marianum) meal (MTM) on egg quality traits, oxidative stability, blood biochemical parameters and liver health indices in laying hens receiving diets supplemented with lipid from different sources. For this purpose, Leghorn laying hens (Hy-Line W-36) were randomly assigned to 12 experimental treatments with eight replicates of five birds each. Dietary treatments consisted of four dietary fat sources (fish oil, sunflower oil, poultry oil and fat powder, each with different fatty acid profiles) and three levels of MTM (0.0, 15 and 30g/kg) offered through 10days of adaptation and 70days of main recording. Results showed that dietary inclusion of polyunsaturated fatty acids, including fish or sunflower oils, reduced serum cholesterol content but increased blood malondialdehyde (MDA) concentration (p<0.05). While fish oil improved the yolk colour index and Haugh unit (p<0.05), it decreased yolk cholesterol concentration (p<0.01). The highest hepatic glycogen content and tissue integrity as well as the lowest liver lipid percentage and MDA content were observed in birds fed diets supplemented with poultry oil. On the other hand, feeding 30g/kg of MTM reduced not only hepatic lipid percentage but also aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities (p<0.01), while it improved eggshell strength and thickness (p<0.05). Supplementation of fat powder enhanced hepatic C16:0 content, while addition of poultry, sunflower or fish oil increased C18:1, C18:2 or C20:5 concentrations respectively (p<0.01); nonetheless, feeding the highest level of MTM reduced hepatic ΣSFA but increased Σn-3 fatty acids (p<0.01). The interaction effects indicated that fish or sunflower oil supplementation increased the MTM level required to reduce not only serum or egg cholesterol concentrations (p<0.05) but also blood or hepatic MDA content (p<0.01). It was concluded that fish oil and MTM (30g/kg) supplements might improve internal egg quality traits and eggshell quality respectively. The hepatic fatty acid profile was also found strongly correlated with dietary fatty acids. Finally, the best hepatic health indices and the highest oxidative stability were achieved when the birds were fed diets supplemented with poultry oil and 30g/kg of MTM.