Effect of nano yam polysaccharide on the blood glucose and blood lipid in rats.

Chinese yam is the dry rhizome of dioscoreaceae plant. Polysaccharide in yam is one of significant functional components, its pharmacological effects include glucose-lowering, lipid-lowering, anti-tumor, anti-oxidation and enhancing the immune. The effects of nano yam polysaccharide on the metabolism of blood glucose and blood lipid in model rats were systematically investigated in this study. The results showed that the diabetic rat model can been successfully induced by the peritoneal injection of 200mg/kg alloxan. The rats were fed with the high-fat diet for 30d, which could induce a model of hyperlipidemia rat successfully. After the model rats were fed with nano yam polysaccharide of 50mg/ml and 100mg/ml per day for 12d and 30d, respectively. For each nano yam polysaccharide group, the blood glucose level was significantly reduced, the glucose tolerance, glycogen and the content of C-peptide were improved in alloxan rats. Moreover, the symptom of one little and three more in diabetic rats was ameliorated and the contents of TC, TG and LDL-C in the serum for the high fat rats were significantly decreased.

Effects of Sideritis scardica Extract on Glucose Tolerance, Triglyceride Levels and Markers of Oxidative Stress in Ovariectomized Rats.

Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells.

Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB.

Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) are critically involved in the etiopathology of amebic liver abscess (ALA). In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA) decreased infection, propranolol (ß-adrenergic blocker) treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker) significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) were increased at 12 h post-infection. Chemical denervation and α and ß-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG) and decreased both reduced glutathione (GSH) and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1ß (IL-1ß), and showed a tendency to decrease hemoxigenase-1 (HO-1), but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1ß, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1ß were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.

Antioxidant and anti-fatigue activities of egg white peptides prepared by pepsin digestion.

BACKGROUND: Some hydrolyzed peptides derived from food proteins possess antioxidant and anti-fatigue activities. In this study, egg white protein powder (EWPP) was hydrolyzed with pepsin for various times, and four peptide fractions were separated from the hydrolysates by ultrafiltration. The antioxidant activity of the four peptide fractions was determined. The peptide fraction with the strongest antioxidant activity was used to evaluate its anti-fatigue effect and probable mechanisms. RESULTS: The egg white peptides (EWPs) fraction with molecular weight 2-5 kDa (named EWPs2) showed stronger antioxidant activity than the other peptide fractions (P < 0.05). The swimming time to exhaustion of mice administered EWPs2 was longer (P < 0.05) than that of the control group. EWPs2 increased the levels of blood glucose (by 28.4-42.2%), muscle glycogen (by 6.4-10.6%) and liver glycogen (by 10.7-23.8%) and significantly decreased the levels of lactic acid in muscle and urea nitrogen in blood (P < 0.05). CONCLUSION: Among the four peptide fractions, EWPs2 possessed the strongest antioxidant activity and exhibited an anti-fatigue effect. The experimental data could clarify partially the anti-fatigue mechanisms of EWPs and provide an important basis for developing EWPs as safe and natural antioxidants and anti-fatigue agents for wide use.

Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion.

BACKGROUND: This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion. METHODS: Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion+sildenafil (SIL; sildenafil gavaged at 50mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA). RESULTS: The ALT and AST levels were highest in the IR group and were lower in the SIL group (p<0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p<0.05) and higher than in the SIL group (p>0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p<0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue. CONCLUSIONS: Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels.

Intermittent sustained swimming in 'matrinxã' Brycon amazonicus (Bryconidae: Bryconinae): hematological and metabolic responses

In fish, studies on a wide variety of physiological effects of exercise have been reported since a long time. It has been attributed special attention to some types of exercise, however, its application as a healthful practice in the rearing and welfare of farming fish is rising in last few years. In this particular, long-term intermittent sustained swimming (ISS) has been not yet explored. In this work, the freshwater fish Brycon amazonicus was submitted to (ISS) for 30 days at velocity of 1.0 body-length sec-1 for 12h interspaced by 12h under still water. Hematology and metabolism were evaluated. Exercised fish decreased 30% the erythrocyte number and hemoglobin was unvaried. The stores of liver glycogen and muscular triacylglycerol (TAG) were increased and the metabolic profile was typically aerobic. The slight decrease of liver (TAG) plus the full metabolic and hematic trait allow investing in this kind of exercise a beneficial practice in the rearing of fish species.

Há muito tempo, tem sido relatada uma ampla variedade de efeitos fisiológicos em peixes sob exercício. Tem sido dada especial atenção a alguns tipos de exercício, mas, sua aplicação como prática salutar na criação e para o bem estar dos peixes vem crescendo nos últimos anos. Neste caso, a natação sustentada intermitente (ISS) por longos períodos ainda não foi explorada. Neste trabalho, o peixe de água doce Brycon amazonicus foi submetido a (ISS) por 30 dias à velocidade de 1,0 comprimento corporal s-1 por 12h intervalado de 12h sob regime de água sem movimento. A hematologia e o metabolismo foram avaliados. Os peixes exercitados diminuíram 30% a contagem de eritrócitos e o teor de hemoglobina permaneceu constante. Os estoques de glicogênio hepático, o teor de triacil glycerol muscular (TAG) aumentou e o perfil metabólico foi tipicamente aeróbico. O discreto aumento de TAG hepático, além das características hematológicas e do metabolismo como um todo, instiga-nos investigar este tipo de exercício como uma prática benéfica na criação de peixes.

Antihyperglycemic potentials of a threatened plant, Helonias dioica: antioxidative stress responses and the signaling cascade.

Helonias dioica (HD) is a threatened species of herb growing in North America. It is used as a traditional medicine for treating various ailments particularly related to reproductive issues. The root is reported to contain approximately 10% of a saponin (chamaelirin; C(36)H(62)O(18)) apart from certain other fatty acids. As saponins are known to have hypoglycemic effects, we suspected its possible antihyperglycemic potentials. We injected intraperitoneally alloxan (ALX) at the dose of 200 mg/kg body weight (bw) to induce hyperglycemia in mice and tested possible hypoglycemic effects of HD in vivo by deploying two doses (100 and 200 mg/kg bw, respectively). We also tested its effects on the isolated pancreatic islets cells in vitro. We used various standard protocols like reactive oxygen species (ROS) generation and DNA damage, activities of biomarkers like catalase (CAT), superoxide dismutase (SOD), lipid peroxidase (LPO), reduced glutathione (GSH) of the pancreas tissue and glucokinase and glycogen content of the liver of hyperglycemic mice. With a mechanistic approach, we also tracked down the possible signaling pathway involved. We found an elevated level of ROS generation, LPO and overexpression of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), p38 Map kinase (p38 MAPK), nuclear factor (NF)-κß, interferon gamma (IFN-γ), cytochrome c, caspase 3, poly [ADP ribose] polymerase (PARP) and cyclo oxygenase 2 (COX2) in ALX-induced diabetic mouse. Treatment of hyperglycemic mice with both the doses of HD showed a significant decrease with respect to all these parameters of study. Thus, our results suggest that HD prevents ALX-induced islet cell damage and possesses antihyperglycemic and antioxidative potentials.

Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats.

We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia.

Effects of the peroxisome proliferator-activated receptor-alpha agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves.

Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists increase fatty acid oxidation in liver of nonruminants. If similar effects occur in dairy cattle, enhanced hepatic oxidative capacity could decrease circulating nonesterified fatty acids and hepatic triacylglycerol accumulation in periparturient cows. The objectives of this study were 1) to determine whether partitioning of fatty acid metabolism by liver slices from weaned Holstein calves treated with PPARalpha agonists in vivo is altered compared with partitioning by liver slices from control (untreated) calves, and 2) to measure in vitro metabolism of palmitate and oleate by bovine liver slices and relate these to mRNA abundance for key enzymes. Weaned male Holstein calves (7 wk old; n=15) were assigned to 1 of 3 groups for a 5-d treatment period: control (untreated), clofibrate (62.5 mg/kg of BW), or fish oil (250 mg/kg of BW). Calves treated with clofibrate consumed less dry matter. Body weight, liver weight, liver weight:body weight ratio, blood nonesterified fatty acids, beta-hydroxybutyrate, and liver composition were not significantly different among treatments. Liver slices were incubated for 2, 4, and 8 h to determine in vitro conversion of [1-(14)C] palmitate and [1-(14)C] oleate to CO(2), acid-soluble products, esterified products, and total metabolism. In liver slices incubated for 8 h, conversion of palmitate to CO(2) was greater for calves treated with clofibrate compared with control calves or calves treated with fish oil. Conversion of palmitate to esterified products, total palmitate metabolism, and metabolism of oleate were not different among treatments. Conversion of palmitate to CO(2) was greater than that from oleate for all treatments, but rates of total metabolism did not differ. Clofibrate increased or tended to increase liver expression of several PPARalpha target genes involved in fatty acid oxidation (e.g., ACADVL, ACOX1, CPT1A), whereas fish oil did not significantly affect genes associated with fatty acid oxidation but tended to increase DGAT1. Overall, our data indicated that bovine liver responded to clofibrate treatment but not fish oil, although increases in hepatic lipid metabolism were much less than those reported in rodents treated with clofibrate or fish oil. Applications of PPARalpha agonists may be of interest to increase the rate of hepatic fatty acid oxidation and decrease triacylglycerol accumulation in periparturient dairy cows.

Effects of long-term mildronate treatment on cardiac and liver functions in rats.

Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by lowering l-carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long-term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate, l-carnitine and gamma-butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. The l-carnitine-lowering effect of mildronate was dose-dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long-term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.

Effect of garlic (Allium sativum) on nickel II or chromium VI induced alterations of glucose homeostasis and hepatic antioxidant status under sub-chronic exposure conditions.

Garlic (Allium sativum) has a profound effect in reducing plasma glucose and increasing serum insulin in diabetic rats. We studied the effect of a garlic extract on nickel- or chromium-induced alteration of plasma glucose and hepatic glycogen levels and anti-oxidant status in rats. Adult male albino rats (n=36) divided into six groups of six animals each were treated as follows: Group I, untreated controls; Group II, fresh aqueous homogenate of garlic; Group III, nickel sulfate; Group IV, nickel sulfate + garlic; Group V, potassium dichromate; Group VI, potassium dichromate + garlic. In Groups IV and VI, the simultaneous administration of garlic abrogated a significant nickel- or chromium-induced increase in plasma glucose and decrease in liver glycogen. Nickel and chromium alone also increased lipid peroxide (LPO) and decreased glutathione levels, as well as the activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase. Simultaneous garlic administration significantly reduced the LPO level and remarkably improved SOD activity. Hence, we postulate that the administration of garlic can prevent nickel II- or chromium VI-induced alterations in blood glucose homeostasis while exerting a hepatoprotective effect on glycogen levels and antioxidant status in male albino rats.

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats / Associação entre diabetes e exposição à fumaça de cigarro sobre a glicemia e glicogênio hepático de ratas Wistar prenhes

PURPOSE: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. METHODS: 60 adult rats were randomly distributed into (n=10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. RESULTS: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43±0.43), G3 (3.20±0.49), G4 (2.62±0.34), G5 (2.65±0.27) and G6 groups (1.94±0.35) presented decreased liver glycogen concentrations compared to G1 (4.20±0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. CONCLUSIONS: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.

OBJETIVO: Avaliar a associação da exposição à fumaça de cigarro e/ou diabete sobre a glicemia e concentrações de glicogênio hepático em ratas Wistar prenhes. MÉTODOS: 60 ratas adultas foram distribuídas aleatoriamente em seis grupos (n=10/grupo): não-diabético exposto ao ar filtrado (G1); não-diabético exposto à fumaça de cigarro antes da prenhez (G2); não-diabético exposto à fumaça de cigarro antes e durante a prenhez (G3); diabético exposto ao ar filtrado (G4); diabético exposto à fumaça de cigarro antes da prenhez (G5); diabético exposto à fumaça de cigarro antes e durante a prenhez (G6). A glicemia foi determinada nos dias 0 e 21 de prenhez. Foram coletadas amostras de fígado para dosagens de glicogênio. RESULTADOS: No 21º dia de prenhez, a glicemia foi maior nos grupos G5 e G6 comparados ao grupo G4. Os grupos G2 (2,43±0,43), G3 (3,20±0,49), G4 (2,62±0,34), G5 (2,65±0,27) e G6 (1,94±0,35) apresentaram concentrações de glicogênio diminuídas comparados ao grupo G1 (4,20±0,18 mg/100mg) (p <0.05). Os grupos G5 e G6 apresentaram ganho de peso materno e peso da ninhada diminuídos. CONCLUSÕES: O diabete grave e a exposição à fumaça de cigarro, sozinhos ou associados, causaram prejuízo no armazenamento de glicogênio na prenhez a termo. Devido ao fato dos estoques de glicogênio serem determinantes para a tolerância à glicose, é imprescindível indicar um rígido controle glicêmico e deixar de fumar antes da gestação.

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats.

PURPOSE: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. METHODS: 60 adult rats were randomly distributed into (n=10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. RESULTS: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43+/-0.43), G3 (3.20+/-0.49), G4 (2.62+/-0.34), G5 (2.65+/-0.27) and G6 groups (1.94+/-0.35) presented decreased liver glycogen concentrations compared to G1 (4.20+/-0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. CONCLUSIONS: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.

Avaliação do perfil lipídico, glicêmico, conteúdo de glicogênio hepático ecardíaco em ratos diabéticos suplementados com farinha de casca de maracujá (Passiflora edulis) / Assessment of the profile of lipids, glucose, liver and heart glucogen, in diabetic mice supplemented withpassion-fruit rind flour (Passiflora edulis) / Evaluación del perfil de lípidos, glucosa, contenido de glicógeno hepático y cardíaco, en ratones diabéticoscomplementados con harina de cáscara de maracuyá (Pasiflora edulis)

A ingestão de fibras alimentares está associada a redução do risco das complicações do diabetes mellitus, caracterizado pelos níveis elevados de glicose sangüínea. Com base nisto, o presente estudo propôs verificar o efeito da suplementação com farinha de casca de maracujá (Passiflora edulis) sobre os níveis plasmáticos de glicose, triglicérides, colesterol total e frações, e conteúdo de glicogênio hepático e cardíaco de ratos diabéticos. Utilizou-se 25 ratos, divididos em 5 grupos (n=5): grupo controle (GI) e grupo diabético (GII) que receberam ração comercial, dois grupos diabéticos tratados com ração suplementada com farinha de maracujá nas concentrações de 50 (GIII) e 100% (GIV) da dose correspondente à ingestão diária recomendada (IDR) de fibras, e grupo GV com ração suplementadacom 150% da IDR. Após o tratamento, coletou-se o plasma sangüíneo para análise dos parâmetros bioquímicos. No fígado e no coração, dosou-se o conteúdo de glicogênio. Em relação aos níveis lipídicos, não houve diferença significativa entre os grupos. A glicemia do GIII (137,60 ± 10,24 mg/dL)e GIV (153,60 ± 14,99 mg/dL) foi reduzida quando comparada ao GII (399,20 ± 37,21 mg/dL). O teor de glicogênio hepático e cardíaco, respectivamente, em GIII (22,91 ± 7,78 mg/g e 0,65 ± 0,09 mg/g)e GIV (28,29 ± 7,99 mg/g e 2,1 ± 0,19 mg/g) aumentou significativamente em relação ao GI (7,0 ± 4,71mg/g e 0,12 ± 0,01 mg/g), p<0,05. Conclui-se que a utilização da farinha de casca de maracujá nas concentrações de 50 e 100% da IDR foi efetiva para controle glicêmico e aumento do glicogênio hepático e cardíaco, não sendo efetiva na diminuição de lipídios plasmáticos no período de estudo.

The intake of alimentary fibers is associated to the reduction of the risk of complications with diabetes mellitus, which is characterized by high glucose levels in the blood. Based upon this,the present study aimed to check the effect of supplementation with passion fruit rind flour (Pasiflora edulis) on the glucose plasmatic levels, triglycerides, cholesterol total and fractions, and the hepatic and heart glucogen in diabetic mice. Twenty five mice were used, divided into 5 groups (n=5): control group (GI) and diabetic group (GII) which received commercial ration,two diabetic groups which received ration supplemented with passion fruit flour, 50% (GIII) and100% (GIV) concentrations of the recommended dose of daily fiber intake (RDI), and group(GV) having ration supplemented with 150% of the RDI. After the treatment, blood plasma was collected for the analysis of the biochemical parameters. The content of glucogen in the liver and the heart was quantified. In relation to the lipidic levels no significant difference was found among groups. The glucose level in GIII (137.60 + 10.24 mg/dL) and in GIV (153.60 + 14.99 mg/dL) was reduced when compared to GII (399.20 + 37.21 mg/dL). The level of hepatic and heart glucogen was significantly increased in GIII (22.91 + 7.71 mg/g and 0.65 + 0.09 mg/g) and GVI (28.29 + 7.99 mg/g) when compared to GI (7.0 + 4.71 mg/g and 0.12 + 0.01 mg/g), p<0.05. It was concluded that the use of flour from passion fruit rind in the concentrations of 50% and 100% was effective on the control of blood glucose and the increase of hepatic and heart glucogen, not being effective on the reduction of plasmatic lipids during the period of study.

La ingestión de fibras alimentares está asociada a la reducción del riesgo de complicaciones de la diabetes mellitus, caracterizada por elevados niveles de glucosa en la sangre. Con base en esto, el presente estudio se propuso verificar el efecto de la complementación con harina de cáscara de maracuyá (Pasiflora edulis) sobre los niveles plasmáticos de glucosa, triglicéridos, colesterol total y fracciones, y contenido de glicógeno hepático y cardíaco en ratones diabéticos. Se utilizaron 25 ratones, divididos en 5 grupos (n=5): grupo de controle (GI) y grupo diabético (GII) que recibieron ración comercial, dos grupos diabéticos tratados con ración complementada con harina de maracuyá, en las concentraciones de 50% (GIII) y 100% (IV) de la dosis correspondiente a la ingestión diaria recomendada (IDR) de fibras, y grupo (GV) con ración complementada con 150% de la IDR. Tras el tratamiento se colectó el plasma de la sangre para el análisis de los parámetros bioquímicos. En el hígado y en el corazón se ha dosificado el contenido de glicógeno. Con relación a los niveles lípidos no hubo diferencia significativa entre los grupos. La glicemia del GIII (137,60 + 10,24 mg/dL) y GIV (153,60 + 14,99 mg/dL)se ha reducido cuando comparada con GII (399,20 + 37,21 mg/dL). El contenido de glicógenohepático y cardíaco, respectivamente, en GIII (22,91 + 7,78 mg/g y 0,65 + 0,09 mg/g) y GIV(28,29 + 7,99 mg/g y 2,1 + 0,19 mg/g) ha aumentado significativamente con relación al GI (7,0+ 4,71 mg/g), p<0,05. Se ha concluido que la utilización de la harina de cáscara de maracuyá,en las concentraciones de 50% y 100% de la IDR, fue efectiva para el control de la glucosa y del aumento del glicógeno hepático y cardíaco, no resultando efectivo en la reducción de lípidos plasmáticos durante el periodo del estudio.

Treadmill exercise reduces obestatin concentrations in rat fundus and small intestine.

Ghrelin and obestatin both are orexigenic/anorexigenic peptides which are secreted from gastrointestinal tracts (fundus submucosa cells). Obestatin is a 23 amino acid peptide recently isolated from rat stomach, is encoded by the same gene that encodes ghrelin. It has been suggested that ghrelin/obestatin stimulate growth hormone release and have opposite actions on food intake. Distribution and biological activity of obestatin and its role in energy balance were studied in rodents. The purpose of the present study was to investigate fundus and intestine obestatin concentrations and selected hormonal responses to a treadmill exercise running program. Fourteen adult Wistar male rats (12-14 weeks old, 235-250 g) were used for this study. Animals were divided into control (n=7) and training (n=7) groups. Training group was given exercise on a motor-driven treadmill at 25 m/min (0% grade) for 60 min/day, 5 days/week for 6 weeks. Rats were sacrificed 48 h after the last session of exercise fundus, small intestine, and liver were excised, immediately washed in ice-cold saline, and frozen in liquid nitrogen for determination of obestatin and ATP concentrations and liver glycogen content. Plasma was collected for glucose, growth hormone (GH), insulin, and cortisol measurements. Total obestatin concentrations were significantly (P<0.045, P<0.032, respectively) low in trained rat fundus and intestine at rest. Fundus and intestine ATP content remained unchanged. Liver glycogen content was significantly (P<0.039) higher in trained rats. Changes in plasma total obestatin, glucose, insulin, cortisol levels were not significant. Plasma GH concentrations was significantly (P<0.001) higher in trained animals when compared with control rats. The data indicate that moderate treadmill exercise was able to reduce fundus and small intestine total obestatin concentrations and this reduction was accompanied with a higher plasma GH and liver glycogen content in trained rats. Exercise training might modulate fundus and intestine total obestatin levels via an improvement of energy source and a negative feedback action of GH on this peptide.

Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism.

Glycogen synthase kinase 3 comprises two isoforms (GSK-3alpha and GSK-3beta) that are implicated in type II diabetes, neurodegeneration, and cancer. GSK-3 activity is elevated in human and rodent models of diabetes, and various GSK-3 inhibitors improve glucose tolerance and insulin sensitivity in rodent models of obesity and diabetes. Here, we report the generation of mice lacking GSK-3alpha. Unlike GSK-3beta mutants, which die before birth, GSK-3alpha knockout (GSK-3alpha KO) animals are viable but display enhanced glucose and insulin sensitivity accompanied by reduced fat mass. Fasted and glucose-stimulated hepatic glycogen content was enhanced in GSK-3alpha KO mice, whereas muscle glycogen was unaltered. Insulin-stimulated protein kinase B (PKB/Akt) and GSK-3beta phosphorylation was higher in GSK-3alpha KO livers compared to wild-type littermates, and IRS-1 expression was markedly increased. We conclude that GSK-3 isoforms exhibit tissue-specific physiological functions and that GSK-3alpha KO mice are insulin sensitive, reinforcing the potential of GSK-3 as a therapeutic target for type II diabetes.

Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0.

Storage of glycogen is essential for glucose homeostasis and for energy supply during bursts of activity and sustained muscle work. We describe three siblings with profound muscle and heart glycogen deficiency caused by a homozygous stop mutation (R462-->ter) in the muscle glycogen synthase gene. The oldest brother died from sudden cardiac arrest at the age of 10.5 years. Two years later, an 11-year-old brother showed muscle fatigability, hypertrophic cardiomyopathy, and an abnormal heart rate and blood pressure while exercising; a 2-year-old sister had no symptoms. In muscle-biopsy specimens obtained from the two younger siblings, there was lack of glycogen, predominance of oxidative fibers, and mitochondrial proliferation. Glucose tolerance was normal.

Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice.

We have evaluated the anti-diabetic effect of a alpha-glucan (MT-alpha-glucan) from the fruit body of maitake mushrooms (Grifola frondosa) on KK-Ay mice (a kind of genetical type 2 diabetes animal model). The effects of MT-alpha-glucan (450 or 150 mg kg (-1)) on diabetic mice were investigated by observing the changes in body weight, the level of fasting plasma glucose, glycosylated serum protein (GSP), hepatic glycogen, serum insulin, triglycerides, cholesterol, free fatty acid, liver superoxide dismutase (SOD), glutathione peroxidase (GSHpx), reduced glutathione (GSH) and malondialdehyde (MDA). Moreover, the binding capacity of insulin receptors on liver crude plasma membranes was assayed and histopathological changes in the pancreas were observed. Treatment with MT-alpha-glucan significantly decreased the body weight, level of fasting plasma glucose, GSP, serum insulin, triglycerides, cholesterol, free fatty acid and MDA content in livers. Treatment with MT-alpha-glucan significantly increased the content of hepatic glycogen, GSH and the activity of SOD and GSHpx. Moreover, the insulin binding capacity to liver crude plasma membranes increased and histopathological changes in the pancreas were ameliorated in the treatment group. These data suggest that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice, which might be related to its effect on insulin receptors (i.e., increasing insulin sensitivity and ameliorating insulin resistance of peripheral target tissues).

Effect of fish oil supplementation for 2 generations on changes in macrophage function induced by Walker 256 cancer cachexia in rats.

The effect of coconut fat (rich in medium saturated fatty acids) or fish oil (rich in omega-3 polyunsaturated fatty acids) supplementation for 2 generations on tumor growth, cancer cachexia, animal survival and macrophage function was investigated in Walker 256 tumor-bearing rats. Female Wistar rats were supplemented with coconut fat or fish oil prior to mating and then throughout pregnancy and gestation. Both supplementations were daily and orally given at 1 g per kg body weight as a single bolus. Same treatment was performed by the 2 following generations. At 90 days of age, male offspring (50%) from F2 generation were subcutaneously inoculated with 2 x 10(7) Walker 256 tumor cells. At 14 days after tumor implantation, rats not supplemented displayed cancer cachexia characterized by loss of body weight, hypoglycemia, hyperlacticidemia, hypertriglyceridemia, decreased food intake and depletion of glycogen stores in the liver and skeletal muscles. Supplementation with coconut fat did not affect these parameters. However, supplementation with fish oil decreased tumor growth (59%), prevented body weight loss and food intake reduction and attenuated cancer cachexia. In addition, fish oil increased animal survival up to 20 days (from 25% in rats not supplemented to 67% in rats supplemented with fish oil) and improved macrophage function characterized by increased phagocytosis capacity and production of hydrogen peroxide and nitric oxide. These results suggest that fish oil supplementation for 2 generations improves macrophage function in association to reduced tumor growth and attenuated cancer cachexia, maintaining food intake and increasing animal survival.

Antiobesity effects of the beta-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression.

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 microg/kg.d, 22d) reduced food intake and slowed weight gain: approximately 10% (P<0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P<0.05). Whereas PF decreased lean tissue (P<0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean+/-se, 0.82+/-0.0, 0.81+/-0.0, respectively; P<0.05) similar to VEH (0.84+/-0.01). Energy expenditure (EE mean+/-se) tended to be reduced by PF (5.67+/-0.1 kcal/h.kg) and maintained by amylin (5.86+/-0.1 kcal/h.kg) relative to VEH (5.77+/-0.0 kcal/h.kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74+/-0.09 kcal/.kg; P<0.05) relative to VEH (5.49+/-0.06) and PF (5.38+/-0.07 kcal/h.kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P<0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P<0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.