[γ-aminobutyric acid fortified rice alleviated oxidative stress and pancreatic injury in type 2 diabetic mice].

OBJECTIVE: To investigate the effects of gamma aminobutyric acid(GABA) fortified rice diet intervention on oxidative stress and pancreatic injury in type 2 diabetes mellitus(T2 DM) mice. METHODS: Of the 70 male ICR mice, 10 were randomly selected as blank control group and they were always fed with the normal white rice feed. The remaining 60 mice were fed with high-fat white rice for 9 weeks. They were fasted for 12 h and injected intraperitoneally with streptozocin(STZ) at a dose of 50 mg/kg body weigh for two consecutive days. The control group was injected with the corresponding volume of normal saline. Subsequently, 50 T2 DM mice with successful modeling were randomly divided into 5 groups according to blood glucose, 10 in each group: T2 DM model control group, germinated brown rice positive control group(GABA content is 0. 2 g/kg feed), GABA-fortified rice low, medium and high dose group(GABA content was 0. 02, 0. 1 and 0. 2 g/kg feed respectively) and each target diet was fed for 6 weeks. Oral glucose tolerance test was performed one week before the end of the experiment to observe the hypoglycemic effect of different doses of GABA fortified rice. After the end of the experiment, HE staining was used to observe the morphology of pancreas. At the same time, the redox indicators from plasma and pancreas of reactive oxygen species(ROS), malondialdehyde(MDA), total antioxidant capacity(T-AOC), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) were examined in each group; The mRNA expressions of oxidative stress-related genes including glycogen synthase kinase-3ß(GSK-3ß), nuclear transcription factor 2(Nrf2), heme oxygenase 1(HO-1) and NAD(P)H: quinone oxidoreductase1(NQO1), insulin secretion related genes including pancreatic and duodenal homeobox 1(PDX-1), mus musculus v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A(MafA), glucokinase(GCK), glucose transporter 2(GLUT2) and the apoptosis associated genes including b-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax) and caspase-3 in pancreas were assayed by real-time fluorescent quantitative PCR. RESULTS: The intervention of GABA fortified rice could alleviate the improvement of the blood glucose level and the lack of insulin secretion in T2 DM mice and relieve plasma and pancreatic oxidative stress. besides, The intervention of GABA fortified rice could up-regulate the expression of insulin secretion-related genes PDX-1, GCK, GLUT2, inhibit the expression of pro-apoptotic gene caspase-3 and promote the expression of anti-apoptosis gene Bcl-2. There was a dose-response relationship between the above result and the 0. 2 g/kg dose group was the most significant, which achieved similar result to germinated brown rice. CONCLUSION: GABA-fortified rice can significantly improve the plasma and pancreatic redox status of STZ-induced T2 DM mice, regulate the expression levels of oxidative stress-related genes and apoptosis-related genes, thereby protect pancreatic tissue morphology, improve pancreatic insulin secretion and thereby alleviate glucose metabolism.

Dietary methionine restriction improves glucose metabolism in the skeletal muscle of obese mice.

Dietary methionine restriction (MR) has many positive effects on metabolic health. Recent studies have indicated that overall insulin sensitivity is improved by dietary MR. This study aimed to determine the effects of MR on insulin signalling and glucose utilisation in the skeletal muscle of obese mice. First, male C57BL/6J mice in the CON group were fed a control diet (0.86% methionine + 4% fat) for 34 weeks, and others were fed a high-fat (HF) diet (0.86% methionine + 20% fat) for 10 weeks to induce obesity. Then, the mice were divided into four dietary groups: the HF group (maintained on the HF diet), HF + MR group (0.17% methionine + 20% fat), C* group (changed to a control diet, 0.86% methionine + 4% fat), and C* + MR group (0.17% methionine + 4% fat) for 24 weeks. Mice were euthanised at 8, 16 or 24 weeks. The results indicated that MR ameliorated obesity-induced hyperglycaemia and hyperinsulinemia. Moreover, MR up-regulated the gene expression of disulfide-bond A oxidoreductase-like protein and cystathionine-γ-lyase and promoted adiponectin and H2S production in inguinal white adipose tissue. Furthermore, MR activated AMP-activated protein kinase and inhibited its downstream signalling and up-regulated insulin signalling-related molecules in gastrocnemius muscle. Overall, MR improved glucose metabolism via increasing glycogen synthesis, glycolysis, and aerobic oxidation. Interestingly, most parameters were equivalent between the HF + MR group and C* + MR group. These findings suggest that dietary MR can improve glucose metabolism in obese mice.