RESUMO
The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.
RESUMO
Objective To investigate the association between depression behavior and the expression of calreticulin precursor, tropomyosin I, milogen activated prolein kinase 1 and dual specificity mitogen-activated protein kinase 1 in spontaneous diabetes mellitus rats. Methods Twenty adult male healthy rats (control group) and 40 spontaneous diabetic rats were studied. Forty spontaneous diabetic rats were further divided into diabetes group and diabetic depression group, and the latter was to construct depression model. The depressive behavior of the 3 groups was measured by sucrose water consumption test and wilderness test. The expression level of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogen-activated protein kinase 1 in the hippocampus of the 3 groups was measured by western blot. Results In the 15 th day and 22 nd days of stress, the amount of sucrose water drinking of the rats in diabetic depression group was significantly lower than that of the control group and the diabetes group (P < 0.05) , and there was no significant difference between the control group and the diabetic group (P> 0.05). The score of field test and vertical score in the diabetic depression group were significantly lower than those of the control group and the diabetes group (P < 0.05) , but there was no significant difference between the control group and the diabetic group (P> 0.05). The expression of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogen-activated protein kinase 1 in the hippocampus of diabetic depression group was significantly lower than that in the control group and the diabetic group (P < 0.05) , and there was no significant difference between the control group and the diabetic group (P> 0.05).Conclusions The depressive behavior of spontaneously diabetic rats is associated with the decrease of the expression level of calreticulin precursor, tropomyosin 1, milogen activated prolein kinase 1, and dual specificity mitogenactivated protein kinase 1 in the hippocampus of rats.
RESUMO
BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose tolerance test and pancreatic insulin level measurements were performed at 11 weeks of age. At week 15, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41,012 genes, and then expression of selected genes was confirmed by qRT-PCR. Gene ontology and protein-protein network analyses were performed to demonstrate potentially characteristic gene alterations and key genes in non-obese T2DM. RESULTS: Fasting blood glucose, serum insulin and cholesterol levels were significantly increased, glucose tolerance and insulin sensitivity were significantly impaired in GK rats as compared to controls. In hearts of GK rats, 204 genes showed significant up-regulation and 303 genes showed down-regulation as compared to controls according to microarray analysis. Genes with significantly altered expression in the heart due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1, Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels (e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by non-obese T2DM. Protein-protein interaction analysis demonstrated that Stat is a potential key gene influenced by non-obese T2DM. CONCLUSIONS: Non-obese T2DM alters cardiac gene expression profile. The altered genes may be involved in the development of cardiac pathologies and could be potential therapeutic targets in non-obese T2DM.
