RESUMO
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
Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.
Assuntos
Iodo/metabolismo , Transportadores de Ácidos Monocarboxílicos/fisiologia , Glândula Tireoide/metabolismo , Sistema y+ de Transporte de Aminoácidos/análise , Animais , Regulação para Baixo , Cadeias Leves da Proteína-1 Reguladora de Fusão/análise , Masculino , Transportadores de Ácidos Monocarboxílicos/análise , Transportadores de Ácidos Monocarboxílicos/genética , Ratos , Ratos Wistar , Hormônios Tireóideos/metabolismoRESUMO
Infection with the nematode Nippostrongylus brasiliensis induces various types of cytological alterations in the intestinal villus epithelium. The aim of this study was to analyse the expression of hexose, peptide and amino acid transporters in the small intestinal epithelium after infection. Brown-Norway rats were infected with 2000 N. brasiliensis L3 larvae and villus epithelial cells were isolated at various time points after infection. Expression of hexose transporters Na(+)/glucose cotransporter SGLT1 and glucose transporter GLUT-1, -2 and -5, a peptide transporter (PepT1) and an amino acid transporter (LAT2) was examined by reverse transcription-PCR, Western blotting or immunohistochemistry. Semi-quantitative reverse transcription-PCR studies of separated jejunal epithelial cells showed that expression levels of GLUT5, PepT1 and LAT2 were significantly decreased 7 and 14 days after infection, while these changes were not observed in the ileal epithelium. Although the apical surface glucose transporter SGLT1 showed no significant alteration in mRNA expression, Western blotting analyses of jejunal epithelial cell lysate showed a marked decrease. Contrary to SGLT1, GLUT5, PepT1 and LAT2, expression of GLUT1, which is essential in maintaining high rates of glucose influx, was significantly up-regulated in the jejunal epithelium 7 and 14 days after infection in reverse transcription-PCR as in Western blotting analyses. Immunohistochemical studies showed that GLUT1 immunoreactivity was localised to the basolateral membrane of intestinal epithelial cells 7 days after infection. These results show that N. brasiliensis infection results in an increase in GLUT1 and a decrease in various hexose, amino acid and peptide transporter expression in jejunal epithelial cells. Up-regulation of GLUT1 might be a compensatory response in injured epithelial cells.