RESUMEN
In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 µM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.
Asunto(s)
Glucemia/metabolismo , Dieta con Restricción de Proteínas , Insulina/sangre , Islotes Pancreáticos/metabolismo , Estrés Oxidativo , Desnutrición Proteico-Calórica/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Antioxidantes/farmacología , Catalasa/genética , Catalasa/metabolismo , Modelos Animales de Enfermedad , Regulación Enzimológica de la Expresión Génica , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Peróxido de Hidrógeno/metabolismo , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Masculino , Estado Nutricional , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Desnutrición Proteico-Calórica/sangre , Desnutrición Proteico-Calórica/genética , Desnutrición Proteico-Calórica/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Factores de TiempoRESUMEN
Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10-1000 µg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E ß-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating ß-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats.