RESUMO
BACKGROUND: We have previously reported that ingestion of adenosine (ADN) and adenosine-5'-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of non-obesity-associated insulin resistance. In this study, we investigated the effect of ADN and AMP ingestion on glucose metabolism in mice with high-fat diet-induced obesity. METHODS: Seven-week-old C57BL/6 J mice were administered distilled water (as a control), 10 mg/L ADN, or 13 mg/L AMP via their drinking water for 14 or 25 weeks, during which they were fed a high-fat diet. Oral glucose tolerance test (OGTT) was conducted on 21-week-old mice fasted for 16 h. Insulin tolerance test (ITT) was performed on 22-week-old mice fasted for 3 h. Blood and muscle were collected for further analysis of serum parameters, gene and protein expression levels, respectively. RESULTS: Glucose metabolism in the ADN and AMP groups was significantly improved compared with the control. OGTT and ITT showed that ADN and AMP groups lower than control group. Furthermore, phosphorylation of AMP-activated protein kinase (AMPK) and mRNA levels of genes involved in lipid oxidation were enhanced in the skeletal muscle of ADN- and AMP-treated mice. CONCLUSION: These results indicate that ingestion of ADN or AMP induces activation of AMPK in skeletal muscle and mitigates insulin resistance in mice with high-fat diet-induced diabetes.
Assuntos
Monofosfato de Adenosina/administração & dosagem , Adenosina/administração & dosagem , Glicemia/metabolismo , Hipoglicemiantes/administração & dosagem , Obesidade/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , FosforilaçãoRESUMO
BACKGROUND: Amino acids have been reported to act as modulators of various regulatory processes and to provide new therapeutic applications for either the prevention or treatment of metabolic disorders. The purpose of the present study is to investigate the effects of single oral dose administration and a continuous treatment of L-tryptophan (L-Trp) on the regulation of blood pressure and glucose metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: First, male 9-week-old SHRSP were administered 100 mg L-Trp·kg-1 body weight in saline to the L-Trp group and 0.9% saline to the control group via a gastric tube as a single oral dose of L-Trp. Second, three groups of SHRSP were fed an AIN-93M-based diet supplemented with L-tryptophan (L-Trp) (0, 200, or 1000 mg·kg-1 diet) for 3 weeks as continuous treatment of L-Trp. RESULTS: Single oral dose administration of L-Trp improved blood pressure, blood glucose, and insulin levels. Blood pressure, blood glucose, and insulin levels improved significantly in the L-Trp treatment groups. The administration of L-Trp also significantly increased plasma nitric oxide and serotonin levels. CONCLUSION: L-Trp by both single oral dose administration and continuous treatment improves glucose metabolism and blood pressure in SHRSP.