RESUMO

The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

Assuntos

Caspase 3/metabolismo , Dieta com Restrição de Proteínas , Carboidratos da Dieta/farmacologia , Músculo Esquelético/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Ubiquitina/metabolismo , Aminoácidos/sangue , Animais , Catepsina B/metabolismo , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/farmacologia , Resistência à Insulina , Masculino , Proteínas Musculares/biossíntese , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptor de Insulina/metabolismo , Proteínas Ligases SKP Culina F-Box/biossíntese , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/biossíntese

RESUMO

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500 mg/kg of metformin and diabetic treated with 250 or 500 mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500 mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500 mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50 µg/mL of ClEtOH, similarly to the incubation with metformin (50 µg/mL) or quercetin (10 µg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin.