RESUMO
Coffee effects on glucose homeostasis in obesity remain controversial. We investigated whether coffee mitigates the negative effects on glucose metabolism induced by a high-fat diet and the interrelationships with redox-inflammatory responses. Rats were treated with: control (CT-); coffee (CT+) 3.9 g of freeze-dried coffee/kg of diet; high-fat (HF-); or high-fat + coffee 3.9 g of freeze-dried coffee/kg of diet (HF+) diet. The high-fat diet increased weight gain, feed efficiency, HOMA ß, muscle and hepatic glycogen, intestinal CAT and SOD activity, hepatic protein (CARB) and lipid oxidation (MDA), muscle Prkaa1 mRNA and IL6 levels, and decreased food intake, hepatic GR, GPX and SOD activities, intestinal CARB, intestinal Slc2a2 and Slc5a1 and hepatic Prkaa1 and Prkaa2 mRNA levels, hepatic glucose-6-phosphatase and muscle hexokinase (HK) activities, compared to the control diet. The high-fat diet with coffee increased hepatic GST activity and TNF and decreased IL6 and intestinal glucosidase activity compared with the high-fat diet. The coffee diet increased muscle glycogen, hepatic CARB and PEPCK activity, and decreased hepatic GR and SOD activities and intestinal CARB, compared with the control diet. Coffee increased insulin levels, HOMA IR/ß, FRAP, muscle Prkaa1 mRNA levels and hepatic and muscle phosphofructokinase-1, and it decreased intestinal CAT, hepatic Slc2a2 mRNA levels and muscle HK activity, regardless of the diet type. In conclusion, chronic coffee consumption improves antioxidant and anti-inflammatory responses, but does not ameliorate glucose homeostasis in a high-fat diet-induced obesity model. In addition, coffee consumption increases insulin secretion and promotes muscle glycogen synthesis in rats maintained on a control diet.
Assuntos
Glicemia/metabolismo , Café , Dieta Hiperlipídica , Inflamação/metabolismo , Obesidade/metabolismo , Animais , Antioxidantes/metabolismo , Metabolismo dos Carboidratos , Citocinas/sangue , Glicogênio/biossíntese , Homeostase , Insulina/sangue , Intestino Delgado/metabolismo , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Oxirredução , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Aloe 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 STUDY: The 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 METHODS: The 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. RESULTS: AVCF-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. CONCLUSION: These 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.
Assuntos
Aloe/química , Carboidratos/farmacologia , Glucose/metabolismo , Glicogênio/biossíntese , Fígado/efeitos dos fármacos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Inflamação/sangue , Inflamação/metabolismo , Insulina/sangue , Ilhotas Pancreáticas/efeitos dos fármacos , Fígado/metabolismo , Masculino , Óxido Nítrico/sangue , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
PURPOSE: To investigate the effects of a single session of either peristaltic pulse dynamic leg compressions (PPDC) or local heat therapy (HT) after prolonged intermittent shuttle running on skeletal muscle glycogen content, muscle function, and the expression of factors involved in skeletal muscle remodeling. METHODS: Twenty-six trained individuals were randomly allocated to either a PPDC (n = 13) or a HT (n = 13) group. After completing a 90-min session of intermittent shuttle running, participants consumed 0.3 g·kg-1 protein plus 1.0 g·kg-1 carbohydrate and received either PPDC or HT for 60 min in one randomly selected leg, while the opposite leg served as control. Muscle biopsies from both legs were obtained before and after exposure to the treatments. Muscle function and soreness were also evaluated before, immediately after, and 24 h after the exercise bout. RESULTS: The changes in glycogen content were similar (P > 0.05) between the thigh exposed to PPDC and the control thigh ~90 min (Control: 14.9 ± 34.3 vs PPDC: 29.6 ± 34 mmol·kg-1 wet wt) and ~210 min (Control: 45.8 ± 40.7 vs PPDC: 52 ± 25.3 mmol·kg-1 wet wt) after the treatment. There were also no differences in the change in glycogen content between thighs ~90 min (Control: 35.9 ± 26.1 vs HT: 38.7 ± 21.3 mmol·kg-1 wet wt) and ~210 min (Control: 61.4 ± 50.6 vs HT: 63.4 ± 17.5 mmol·kg-1 wet wt) after local HT. The changes in peak torque and fatigue resistance of the knee extensors, muscle soreness, and the mRNA expression and protein abundance of select factors were also similar (P > 0.05) in both thighs, irrespective of the treatment. CONCLUSIONS: A single 1-h session of either PPDC or local HT does not accelerate glycogen resynthesis and the recovery of muscle function after prolonged intermittent shuttle running.
Assuntos
Glicogênio/biossíntese , Temperatura Alta/uso terapêutico , Dispositivos de Compressão Pneumática Intermitente , Músculo Esquelético/metabolismo , Corrida/fisiologia , Adolescente , Adulto , Feminino , Humanos , Joelho/fisiologia , Masculino , Fadiga Muscular , Proteínas Musculares/metabolismo , Força Muscular , Mialgia/terapia , RNA Mensageiro/metabolismo , Torque , Adulto JovemRESUMO
BACKGROUND: Diabetes mellitus is a chronic metabolic disease characterized by increased blood glucose levels. In order to lower blood glucose, it is important to stimulate glucose uptake and glycogen synthesis in the muscle. (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (HM-chromanone), a constituent isolated from Portulaca oleracea L., exhibits anti-diabetic effects; however, its mechanisms are not yet clearly understood on glucose uptake and glycogen synthesis in muscle cells. PURPOSE: In the present study, we examined the effects of HM-chromanone on glucose uptake into L6 skeletal muscle cells and elucidated the underlying mechanisms. METHODS: The effects of HM-chromanone on glucose uptake into L6 skeletal muscle cells were assessed by 2-Deoxyglucose uptake assay. Western blot analysis was carried out to elucidate the underlying molecular mechanisms. RESULTS: We found that HM-chromanone promoted glucose uptake into L6 skeletal muscle cells in a dose-dependent manner. Moreover, HM-chromanone induced the phosphorylation of IRS-1Tyr612 and AKTSer473, and the activation of PI3K. HM-chromanone also stimulated the phosphorylation of AMPKThr172, AS160Thr642, TBC1D1Ser237, and ACC via the CaMKKß pathway. Furthermore, HM-chromanone increased glycogen synthesis through the inactivation of glycogen synthase kinase 3 α/ß. CONCLUSION: The results of this study indicate that HM-chromanone stimulates glucose uptake through the activation of the PI3K/AKT and CaMKKß-AMPK pathways and glycogen synthesis via the GSK3 α/ß pathway in L6 skeletal muscle cells.
Assuntos
Flavonoides/farmacologia , Glucose/metabolismo , Glicogênio/biossíntese , Músculo Esquelético/efeitos dos fármacos , Portulaca/química , Animais , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Desoxiglucose/metabolismo , Glicogênio/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
The prolonged impairment in muscle strength, power, and fatigue resistance after eccentric exercise has been ascribed to a plethora of mechanisms, including delayed muscle refueling and microvascular and mitochondrial dysfunction. This review explores the hypothesis that local heat therapy hastens functional recovery after strenuous eccentric exercise by facilitating glycogen resynthesis, reversing vascular derangements, augmenting mitochondrial function, and stimulating muscle protein synthesis.
Assuntos
Exercício Físico/fisiologia , Temperatura Alta/uso terapêutico , Músculo Esquelético/lesões , Mialgia/terapia , Adaptação Fisiológica , Animais , Glicogênio/biossíntese , Humanos , Microcirculação , Mitocôndrias Musculares/fisiologia , Fadiga Muscular/fisiologia , Proteínas Musculares/biossíntese , Força Muscular/fisiologia , Músculo Esquelético/irrigação sanguínea , Mialgia/etiologiaRESUMO
The novel partial nitrification endogenous denitrification and phosphorus removal (PNEDPR) process can achieve deep-level nutrient removal from low carbon/nitrogen municipal wastewater without extra carbons. However, its performance is limited by long hydraulic retention time (HRT) and low specific endogenous denitrification rate (rNO2). This study aimed at investigating the effects of two improving strategies on PNEDPR. One was decreasing both anaerobic and anoxic reaction time for shortening HRT from 55â¯h to 17.5â¯h. The other was temporarily discharging orthophosphate-rich supernatant for balancing the competition between phosphorus and glycogen accumulating organisms to further raise rNO2 without deterioration of phosphorus removal. Results revealed that, desirable nutrient removal was obtained, as average effluent concentrations of total nitrogen and orthophosphate were 8.4 and 0.5â¯mg/L with their average removal efficiencies of 86.8% and 90.9%. High-throughput sequencing analysis revealed that, Candidatus_Competibacter conducted nitrogen removal endogenous denitrification and Candidatus_Accumulibacter and Tetrasphaera ensured phosphorus removal.
Assuntos
Glicogênio/biossíntese , Fósforo/metabolismo , Eliminação de Resíduos Líquidos/métodos , Carbono/metabolismo , Desnitrificação , Nitrificação , Nitrogênio/metabolismo , Fosfatos/metabolismo , Fósforo/isolamento & purificação , Águas Residuárias/químicaRESUMO
Psidium guajava (PG) is a short shrub or tree cultivated in tropical and subtropical regions around the world. The leaf extract of PG (guava leaf) has been used historically to cure many ailments. However, mechanisms of action of guava leaf in treating diabetes are not fully understood. Effects and underlying mechanisms of guava leaf on gluconeogenesis and glycogenesis in hepatocytes, insulin signaling proteins, liver function markers, and lipid profile in streptozotocin (STZ) injected diabetic Wistar rats were investigated within the current study. PG was given orally at the dose of 100, 200, and 400â¯mg/kg b.w to diabetic rats for the period of 45 days. The results reveal that oral administration of PG (200â¯mg/kg b.w) has considerably raised the levels of insulin, glycogen, hexokinase, glucose-6-phosphatase dehydrogenase and significant (pâ¯<â¯0.05) belittled hepatic markers, gluconeogenic enzymes, and OGTT fasting blood glucose levels. OGTT has shown least statistical significance between the group 5 (200â¯mg/kg b.w) and group 6 and vital difference between group 5 and group 4 (400â¯mg/kg). PG has attenuated the triglycerides, total cholesterol, phospholipids, free fatty acid, and LDL levels and raised HDL levels. PG considerably (pâ¯<â¯0.05) activated IRS-1, IRS-2, Akt, p-Akt, PI3K, GLUT2, AMPK, p-AMPK, and p-ACC, which are the key effector molecules of the PI3K/Akt pathway in STZ rats. The results of our study specify that treatment with PG ameliorated glucose-metabolism and lipid profile in STZ evoked diabetic rats; the rationale ought to be the activation of PI3K/Akt, phosphorylation of AMPK pathway in liver and therefore has beneficial anti-diabetic activity.
Assuntos
Acetil-CoA Carboxilase/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Gluconeogênese/efeitos dos fármacos , Glicogênio/biossíntese , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Quinases/metabolismo , Psidium/química , Quinases Proteína-Quinases Ativadas por AMP , Animais , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Fígado/metabolismo , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ratos Wistar , Transdução de Sinais , EstreptozocinaRESUMO
C-Phycocyanin (C-PC), a kind of blue protein isolated from Spirulina platensis, can ameliorate hyperglycemia, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of C-PC on gluconeogenesis and glycogenesis in insulin resistant hepatocytes. Insulin resistance was induced by high glucose (HG) in human hepatocellular carcinoma (HepG2) cells. C-PC ameliorated glucose production and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in HG-induced insulin resistant HepG2 cells. It also increased glucose uptake, glycogen content and glycogen synthase (GS) activation in HG-induced insulin resistant HepG2 cells. The data revealed the mechanism of C-PC in improving glucose homoeostasis via activating the IRS/PI3 K/Akt and SIRT1/LKB1/AMPK signaling pathway in insulin resistant hepatocytes. C-PC could be a promising leading compound for the development of a hypoglycemic agent.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Gluconeogênese/efeitos dos fármacos , Glicogênio/biossíntese , Resistência à Insulina , Fígado/efeitos dos fármacos , Ficocianina/farmacologia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Regulação para Baixo/efeitos dos fármacos , Glucose/biossíntese , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Fígado/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Spirulina/químicaRESUMO
ADP-glucose pyrophosphorylase (AGPase) is a key allosteric enzyme in plant starch biosynthesis. Plant AGPase is a heterotetrameric enzyme that consists of large (LS) and small subunits (SS), which are encoded by two different genes. In this study, we showed that the conversion of Glu to Gly at position 370 in the LS of AGPase alters the heterotetrameric stability along with the binding properties of substrate and effectors of the enzyme. Kinetic analyses revealed that the affinity of the LSE370GSSWT AGPase for glucose-1-phosphate is 3-fold less than for wild type (WT) AGPase. Additionally, the LSE370GSSWT AGPase requires 3-fold more 3-phosphogyceric acid to be activated. Finally, the LSE370GSSWTAGPase is less heat stable compared with the WT AGPase. Computational analysis of the mutant Gly-370 in the 3D modeled LS AGPase showed that this residue changes charge distribution of the surface and thus affect stability of the LS AGPase and overall heat stability of the heterotetrameric AGPase. In summary, our results show that LSE370 intricately modulate the heat stability and enzymatic activity of potato the AGPase.
Assuntos
Glucose-1-Fosfato Adenililtransferase/fisiologia , Proteínas de Plantas/fisiologia , Solanum tuberosum/enzimologia , Amido/biossíntese , Sítios de Ligação , Estabilidade Enzimática , Glucose-1-Fosfato Adenililtransferase/química , Glicogênio/biossíntese , Temperatura Alta , Cinética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Proteínas de Plantas/química , Estrutura Terciária de Proteína , Solanum tuberosum/genética , Especificidade por SubstratoRESUMO
The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation.
Assuntos
Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Proteína Fosfatase 2/metabolismo , Urtica dioica/química , Animais , Composição Corporal , Peso Corporal , Linhagem Celular , Dieta Hiperlipídica , Glucose/metabolismo , Glicogênio/biossíntese , Insulina/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Transdução de SinaisRESUMO
Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic ß-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic ß-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Deficiência de Magnésio/metabolismo , Magnésio/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Glicemia/metabolismo , Canais de Cálcio Tipo L/metabolismo , Diabetes Mellitus Tipo 2/complicações , Suplementos Nutricionais , Progressão da Doença , Glucoquinase/metabolismo , Glicogênio/biossíntese , Glicólise , Humanos , Inflamação , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Canais KATP/metabolismo , Fígado/metabolismo , Magnésio/uso terapêutico , Deficiência de Magnésio/tratamento farmacológico , Obesidade/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Simportadores de Cloreto de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Desequilíbrio Hidroeletrolítico/tratamento farmacológicoRESUMO
BACKGROUND: Glucose-lowering effects of Moringa oleifera extracts have been reported. However, the mechanism for its hypoglycemic effects is not yet understood. This study investigated the effect of oral administration of methanolic extracts of M. oleifera (MOLE) on glucose tolerance, glycogen synthesis, and lipid metabolism in rats with alloxan-induced diabetes. METHODS: MOLE was screened for key phytochemicals and its total flavonoids and phenolic contents were quantified. Diabetes was induced by intraperitoneal injection of 120 mg/kg BW alloxan. Normal and diabetic control rats received saline, while rats in other groups received 300 or 600 mg/kg body weight of MOLE or metformin (100 mg/kg body weight of metformin) for 6 weeks. Food intake and body weight were monitored throughout the experiment. Intraperitoneal glucose tolerance was assessed and serum glucose, insulin, and lipids were measured at the end of the experiment. Liver and muscle glycogen synthase activities, glycogen content, and glucose uptake were determined. RESULTS: Administration of MOLE did not affect food intake but inhibited weight loss, significantly (p<0.01) improved glucose tolerance, and increased serum insulin levels by 1.3-1.7-fold (p<0.01). MOLE treatment significantly (p<0.001) reduced serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and enhanced serum level of high-density lipoprotein (HDL) by 2.4- to 3.2-fold (p<0.001). Glycogen synthase activities and glycogen contents were higher in MOLE-treated rats compared with rats receiving metformin or saline and the extract improved glucose uptake by 49%-59% (p<0.01). CONCLUSIONS: These results showed that hypoglycemic effects of MOLE might be mediated through the stimulation of insulin release leading to enhanced glucose uptake and glycogen synthesis.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Aloxano , Animais , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Glicogênio/biossíntese , Glicogênio Sintase/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metformina/farmacologia , Metanol/química , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos WistarRESUMO
CONTEXT: Antidesma bunius L (Phyllanthaceae) is commonly known to local people in North-east Thailand as a medicinal plant. OBJECTIVES: To investigate hypoglycaemic activities of methanolic extract of A. bunius in type 1 diabetes. MATERIALS AND METHODS: A daily dose of A. bunius extract (250 mg/kg body weight) was given orally to alloxan-induced diabetic rats for 28 days. Blood glucose, insulin, TC, TG, amylase, lipase, liver glycogen were analysed. RESULTS: Extract revealed a significant reduction in blood glucose level (80.5%) along with an increase in serum insulin (134%), lipase (90.7%) and liver glycogen level (160%). Also amylase (28.2%) activity, TC (40.2%), and TG (28.8%) levels were significantly decreased when compared with diabetic control rats. A. bunius extract improved the histo-architectural of the ß-cells. DISCUSSION AND CONCLUSION: The results suggested that A. bunius extract possess anti-diabetic activity, through the enhancement of hepatic glycogen storage and regeneration of the islet of Langerhans.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Malpighiaceae/química , Fitoterapia , Extratos Vegetais/química , Aloxano , Amilases/sangue , Animais , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Feminino , Glicogênio/agonistas , Glicogênio/biossíntese , Humanos , Insulina/sangue , Células Secretoras de Insulina/patologia , Dose Letal Mediana , Lipase/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Plantas Medicinais , RatosRESUMO
QRFP is expressed in central and peripheral regions important for nutrient intake and metabolism. Central administration of QRFP-26 and QRFP-43 induces a macronutrient specific increase in the intake of high fat diet in male and female rats. Recently, cell culture models have indicated that QRFP-26 and QRFP-43 are involved in glucose and fatty acid uptake in pancreatic islets and adipocytes. Since skeletal muscle is a major consumer of circulating glucose and a primary contributor to whole body metabolism, the current study examined the effects of QRFP-26 and QRFP-43 on insulin-stimulated uptake of glucose in skeletal muscle using L6 myotubes. The current experiments were designed to test the hypothesis that QRFP and its receptors, GPR103a and GPR103b are expressed in L6 myotubes and that QRFP-26 and QRFP-43 affect insulin-stimulated uptake of glucose in L6 myotubes. The results indicate that prepro-QRFP mRNA and GPR103a mRNA are expressed in L6 cells, though GPR103b mRNA was not detected. Using complementary assays, co-incubation with QRFP-26, increased insulin's ability to induce glycogen synthesis and 2-deoxyglucose uptake in L6 cells. These data suggest that QRFP-26, but not QRFP-43, is involved in the metabolic effects of skeletal muscle and may enhance insulin's effects on glucose uptake in skeletal muscle. These data support a role for QRFP as a modulator of nutrient intake in skeletal muscle.
Assuntos
Glucose/metabolismo , Músculo Esquelético/metabolismo , Peptídeos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Feminino , Glicogênio/biossíntese , Humanos , Insulina/administração & dosagem , Insulina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Peptídeos/administração & dosagem , RNA Mensageiro/biossíntese , Ratos , Receptores Acoplados a Proteínas G/biossínteseRESUMO
Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration.
Assuntos
Astrócitos/fisiologia , Respiração Celular/efeitos dos fármacos , Glucose/metabolismo , Azul de Metileno/farmacologia , Fármacos Neuroprotetores/farmacologia , Trifosfato de Adenosina/biossíntese , Animais , Astrócitos/efeitos dos fármacos , Hipóxia Celular , Sobrevivência Celular , Células Cultivadas , Citoproteção , Avaliação Pré-Clínica de Medicamentos , Glicogênio/biossíntese , Hexoquinase/metabolismo , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Consumo de OxigênioRESUMO
Present study examined the effects of conjugated linoleic acid (CLA) supplementation on glycogen resynthesis in exercised human skeletal muscle. Twelve male participants completed a cross-over trial with CLA (3.8 g/day for 8 week) or placebo supplements by separation of 8 weeks. CLA is a mixture of trans-10 cis-12 and cis-9 trans-11 isomers (50:50). On experiment day, all participants performed 60-min cycling exercise at 75% VO2 max, then consumed a carbohydrate meal immediately after exercise and recovered for 3 h. Biopsied muscle samples from vastus lateralis were obtained immediately (0 h) and 3 h following exercise. Simultaneously, blood and gaseous samples were collected for every 30 min during 3-h recovery. Results showed significantly increased muscle glycogen content with CLA after a single bout of exercise (P < 0.05). Muscle glucose transporter type 4 expression was significantly elevated immediately after exercise, and this elevation was continued until 3 h after exercise in CLA trial. However, P-Akt/Akt ratio was not significantly altered, while glucose tolerance was impaired with CLA. Gaseous exchange data showed no beneficial effect of CLA on fat oxidation, instead lower non-esterified fatty acid and glycerol levels were found at 0 h. Our findings conclude that CLA supplementation can enhance the glycogen resynthesis rate in exercised human skeletal muscle.
Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Glicogênio/biossíntese , Ácidos Linoleicos Conjugados/administração & dosagem , Músculo Esquelético/metabolismo , Glicemia/metabolismo , Estudos Cross-Over , Ácidos Graxos não Esterificados/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Homeostase , Humanos , Insulina/sangue , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Ventilação Pulmonar , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Khaya senegalensis A. Juss (Meliaceae) is commonly exploited for the traditional treatment of diabetes mellitus in Nigeria and Togo. The present study was conducted to examine the anti-diabetic activity of Khaya senegalensis butanol fraction (KSBF) of root ethanolic extract in a type 2 diabetes (T2D) model of rats. MATERIALS AND METHODS: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were treated with 150 and 300 mg/kg body weight (BW) of the fraction for five days in a week. Relevant diabetes-related parameters were analyzed in all experimental animals. RESULTS: The KSBF treatment, at 300 mg/kg BW, significantly (p<0.05) reduced blood glucose level, improved oral glucose tolerance ability and ß-cell function (HOMA-ß), decreased insulin resistance (HOMA-IR), stimulated hepatic glycogen synthesis, ameliorated serum lipids alterations and prevented hepatic and renal damages compared to untreated diabetic rats. Additionally, the fraction insignificantly (p>0.05) improved weight gain, decreased food and fluid intake, stimulated insulin secretion and lowered serum fructosamine concentrations compared to untreated diabetic rats. CONCLUSIONS: Data from this study suggests that orally administered KSBF, at 300 mg/kg BW, possess remarkable anti-type 2 diabetic activity and could ameliorate some diabetes-associated complications and hence can be considered as a source of potential anti-type 2 diabetic medicine.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Meliaceae/química , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Butanóis/química , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Ingestão de Líquidos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Ingestão de Alimentos/efeitos dos fármacos , Glicogênio/biossíntese , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
OBJECTIVES: Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. METHODS: Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. RESULTS: Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. CONCLUSIONS: Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.
Assuntos
Acroleína/análogos & derivados , Encéfalo/efeitos dos fármacos , Eugenol/farmacologia , Fígado/efeitos dos fármacos , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Acroleína/farmacologia , Acroleína/uso terapêutico , Adiposidade/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Cinnamomum zeylanicum/química , Ingestão de Energia , Eugenol/uso terapêutico , Glicogênio/biossíntese , Humanos , Insulina/administração & dosagem , Insulina/fisiologia , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Atividade Motora/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêuticoRESUMO
Eicosapentaenoic acid-enriched phosphatidylcholine was isolated from the sea cucumber Cucumaria frondosa (Cucumaria-PC) and its effects on streptozotocin (STZ)-induced hyperglycemic rats were investigated. Male Sprague-Dawley rats were randomly divided into normal control, model control (STZ), low- and high-dose Cucumaria-PC groups (STZ + Cucumaria-PC at 25 and 75 mg/Kg·b·wt, intragastrically, respectively). Blood glucose, insulin, glycogen in liver and gastrocnemius were determined over 60 days. Insulin signaling in the rats' gastrocnemius was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The results showed that Cucumaria-PC significantly decreased blood glucose level, increased insulin secretion and glycogen synthesis in diabetic rats. RT-PCR analysis revealed that Cucumaria-PC significantly promoted the expressions of glycometabolism-related genes of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4) in gastrocnemius. Western blotting assay demonstrated that Cucumaria-PC remarkably enhanced the proteins abundance of IR-ß, PI3K, PKB, GLUT4, as well as phosphorylation of Tyr-IR-ß, p85-PI3K, Ser473-PKB (P < 0.05 and P < 0.01). These findings suggested that Cucumaria-PC exhibited significant anti-hyperglycemic activities through up-regulating PI3K/PKB signal pathway mediated by insulin. Nutritional supplementation with Cucumaria-PC, if validated for human studies, may offer an adjunctive therapy for diabetes mellitus.
Assuntos
Cucumaria/química , Ácido Eicosapentaenoico/farmacologia , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Fosfatidilcolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Glicemia/análise , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Ácido Eicosapentaenoico/isolamento & purificação , Ativação Enzimática/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Glicogênio/biossíntese , Glicogênio/metabolismo , Hiperglicemia/induzido quimicamente , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Secreção de Insulina , Masculino , Músculo Esquelético/metabolismo , Fosfatidilcolinas/química , Fosfatidilcolinas/isolamento & purificação , Fosfatidilinositol 3-Quinases/biossíntese , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/biossíntese , Ratos , Ratos Sprague-Dawley , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
The beneficial effects of green tea polyphenols (GTP) against metabolic syndrome and type 2 diabetes by suppressing appetite and nutrient absorption have been well reported. However the direct effects and mechanisms of GTP on glucose and lipid metabolism remain to be elucidated. Since the liver is an important organ involved in glucose and lipid metabolism, we examined the effects and mechanisms of GTP on glycogen synthesis and lipogenesis in HepG2 cells. Concentrations of GTP containing 68% naturally occurring (-)-epigallocatechin-3-gallate (EGCG) were incubated in HepG2 cells with high glucose (30 mM) under 100 nM of insulin stimulation for 24 h. GTP enhanced glycogen synthesis in a dose-dependent manner. 10 µM of EGCG significantly increased glycogen synthesis by 2fold (P < 0.05) compared with insulin alone. Western blotting revealed that phosphorylation of Ser9 glycogen synthase kinase 3 ß and Ser641 glycogen synthase was significantly increased in GTP-treated HepG2 cells compared with nontreated cells. 10 µM of EGCG also significantly inhibited lipogenesis (P < 0.01). We further demonstrated that this mechanism involves enhanced expression of phosphorylated AMP-activated protein kinase α and acetyl-CoA carboxylase in HepG2 cells. Our results showed that GTP is capable of enhancing insulin-mediated glucose and lipid metabolism by regulating enzymes involved in glycogen synthesis and lipogenesis.