RESUMO
The present study investigated the effects of acute melatonin administration on the biomarkers of energy substrates, GLUT4, and FAT/CD36 of skeletal muscle and its performance in rats subjected to exhaustive swimming exercise at an intensity corresponding to the maximal aerobic capacity (tlim). The incremental test was performed to individually determine the exercise intensity prescription and 48 h after, the animals received melatonin (10 mg·kg-1) or vehicles 30 min prior to tlim. Afterwards, the animals were euthanized 1 or 3 h after the exhaustion for blood and muscles storage. The experiment 1 found that melatonin increased the content of glycogen and GLUT4 in skeletal muscles of the animals that were euthanized 1 (p < 0.05; 22.33% and 41.87%) and 3 h (p < 0.05; 37.62% and 57.87%) after the last procedures. In experiment 2, melatonin enhanced the tlim (p = 0.01; 49.42%), the glycogen content (p < 0.05; 40.03%), GLUT4 and FAT/CD36 in exercised skeletal muscles (F = 26.83 and F = 25.28, p < 0.01). In summary, melatonin increased energy substrate availability prior to exercise, improved the exercise tolerance, and accelerated the recovery of muscle energy substrates after the tlim, possibly through GLUT4 and FAT/CD36.
Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Melatonina/administração & dosagem , Resistência Física/efeitos dos fármacos , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Antígenos CD36/análise , Antígenos CD36/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Tolerância ao Exercício/fisiologia , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/metabolismo , Masculino , Modelos Animais , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Resistência Física/fisiologia , Ratos , Natação/fisiologiaRESUMO
Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a wide variety of clinical conditions, such as cancer, muscle dystrophy and neurodegenerative disorders. Evidence has suggested that creatine supplementation alone, and mainly in combination with exercise training, may improve glucose metabolism in health individuals and insulin-resistant individuals, such as in those with type 2 diabetes mellitus. Creatine itself may stimulate insulin secretion in vitro, improve muscle glycogen stores and ameliorate hyperglycemia in animals. In addition, exercise induces numerous metabolic benefits, including increases in insulin-independent muscle glucose uptake and insulin sensitivity. It has been speculated that creatine supplementation combined with exercise training could result in additional improvements in glucose metabolism when compared with each intervention separately. The possible mechanism underlying the effects of combined exercise and creatine supplementation is an enhanced glucose transport into muscle cell by type 4 glucose transporter (GLUT-4) translocation to sarcolemma. Although preliminary findings from small-scale trials involving patients with type 2 diabetes mellitus are promising, the efficacy of creatine for improving glycemic control is yet to be confirmed. In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps.
Assuntos
Creatina/administração & dosagem , Diabetes Mellitus Tipo 2/terapia , Controle Glicêmico/métodos , Animais , Suplementos Nutricionais , Exercício Físico , Glucose/metabolismo , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/genética , Humanos , Resistência à Insulina , Músculo Esquelético/química , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , RNA Mensageiro/análiseRESUMO
There is a gap in the knowledge regarding the regulation of glucose uptake in skeletal muscle during the development of insulin resistance in the elderly. Rho-Kinase (Rock) signaling has been demonstrated as a crucial mechanism related to glucose metabolism and insulin sensitivity in skeletal muscle. This kinase is involved in the insulin receptor substrate 1 (IRS1) phosphorylation, leading to glucose uptake stimulation in the skeletal muscle; however, the mechanisms elucidating the role of Rock regulation in the context of advanced ages are still limited. In this study, we submitted old Fischer 344 rats to short-term treadmill physical exercise protocol (5â¯days) and evaluated the glucose tolerance and proteins involved with Rock/insulin signaling in the skeletal muscle. Compared to young rats, the old rats showed glucose intolerance, hyperinsulinemia, and decreased phosphorylation in the proteins related to the insulin signaling pathway in the skeletal muscle, without changes in body mass and adiposity. Otherwise, when these rats were submitted to physical exercise, it was found decreased fasting glucose, higher glucose tolerance, decreased insulinemia, and upregulation of Rock2/pIRS1/pAkt/pGSK3ß/GLUT4 pathway in the skeletal muscle. In summary, the aging process did not change Rock signaling, but the physical exercise was able to increase Rock2 content and insulin signaling pathway in the skeletal muscle. This finding suggests the benefic role of physical exercise to advanced ages, promoting insulin-sensitive effects with Rho-kinase contribution.
Assuntos
Glucose/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Quinases Associadas a rho/fisiologia , Animais , Transportador de Glucose Tipo 4/análise , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Masculino , Ratos , Ratos Endogâmicos F344 , Transdução de Sinais/fisiologia , Regulação para CimaRESUMO
Skeletal muscle (SM) is the most abundant tissue and the largest reservoir of protein in the body. It transports glucose in an insulin dependent manner by the glucose transporter type 4 (GLUT4) and contributes in the maintenance of serum amino acids concentration. By its mass and energetic requirements, it is fundamental for the systemic metabolic balance. In the present work, we present the effect of gestational undernourishment (GU) on the mechanical and metabolic properties of SM at birth and in old age in an animal model. Mechanical studies were performed on isolated muscles, while the GLUT4, amino acid transporters LAT2, SNAT2 and insulin receptors (IR) determination were performed on isolated transverse-tubule membranes (TT). The GU in offspring at birth, results in low muscle mass with increased contraction force and resistance to fatigue. However, in two-years old rats, there was muscle hypotrophy and sarcopenia, the force decreased between 50 and 70% in control rats and rats with GU respectively, accompanied by a lower expression of LAT2, SNAT2 and IR in TT. In conclusion, GU irreversibly affects the SM, an effect that could be similar in humans, which help us to understand the events that associate the GU with the metabolic debacle of SM and the metabolic diseases of human adulthood.
Assuntos
Desnutrição/complicações , Músculo Esquelético/fisiopatologia , Atrofia Muscular/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Sarcopenia/etiologia , Fatores Etários , Sistema A de Transporte de Aminoácidos , Sistema y+ de Transporte de Aminoácidos/análise , Sistemas de Transporte de Aminoácidos/análise , Aminoácidos/sangue , Animais , Feminino , Cadeias Leves da Proteína-1 Reguladora de Fusão/análise , Glucose , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/metabolismo , Humanos , Modelos Animais , Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/química , Músculo Esquelético/patologia , Gravidez , Ratos , Receptor de Insulina/análiseRESUMO
BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris) contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipogenic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV) by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-γ2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ2, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.
Assuntos
Células 3T3-L1/efeitos dos fármacos , Chlorella vulgaris/química , Extratos Vegetais/farmacologia , Alga Marinha/química , Células 3T3-L1/fisiologia , Proteínas Quinases Ativadas por AMP/análise , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/análise , Adiponectina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Expressão Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Camundongos , PPAR gama/análise , PPAR gama/efeitos dos fármacos , PPAR gama/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris) contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipo-genic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV) by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-y2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.
Assuntos
Animais , Camundongos , Alga Marinha/química , Extratos Vegetais/farmacologia , Células 3T3-L1/efeitos dos fármacos , Chlorella vulgaris/química , Fatores de Tempo , Regulação para Baixo , Expressão Gênica , Diferenciação Celular/efeitos dos fármacos , Regulação para Cima , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células 3T3-L1/fisiologia , PPAR gama/análise , PPAR gama/efeitos dos fármacos , PPAR gama/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Adiponectina/análise , Adiponectina/metabolismo , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Proteínas Quinases Ativadas por AMP/análise , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismoRESUMO
Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin. Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone- and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model.
Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Resistência à Insulina , Animais , Peptídeo C/análise , Ácidos Graxos não Esterificados/sangue , Glucose/metabolismo , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/genética , Glicerídeos/sangue , Lipólise/efeitos dos fármacos , Masculino , Pioglitazona , RNA Mensageiro/análise , Ratos , Ratos Wistar , Estreptozocina , Tiazolidinedionas/farmacologiaRESUMO
The purpose of this study was to analyze the interaction between caloric restriction (CR) and the dwarf mutation at the level of insulin sensitivity and signal transduction. To this end, we analyzed the in vivo status of the insulin signaling system in skeletal muscle from Ames dwarf (df/df) and normal mice fed ad libitum or subjected to short-term (20-day) CR. We measured insulin-stimulated phosphorylation of the IR and IRS-1, IRS-1-p85 association and Akt activation, and the abundance of the IR, IRS-1, p85, GLUT-4 and IGF-1 receptor in skeletal muscle. In terms of glucose homeostasis, the response to CR was different in both groups of animals. In normal animals, CR induced a significant reduction in both circulating insulin and glucose levels, while CR did not modify these parameters in df/df mice. We did not find any significant alteration in either activation or abundance of signaling molecules analyzed after short-term CR in either normal or Ames dwarf mice. We conclude that the initial adaptation to CR in normal mice is an increase in insulin sensitivity without changes in insulin signal transduction, and that this adaptation is not evidenced in df/df mice, probably since they are already hypersensitive to insulin.