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

Abstract

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-3β(GSK-3β), 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.

Keywords: germinated brown rice; oxidative stress; pancreas protection; type 2 diabetes; γ-aminobutyric acid.