The Effect of 12 Weeks Aerobic Training on PDX-1 and GLUT2 Gene Expression in the Pancreatic Tissue of Type 2 Diabetic Rats

Objective: The aim of this study was to investigate the effect of 12 weeks aerobic training on PDX-1 and GLUT2 gene expression in the pancreatic tissue of type 2 diabetic rats. Materials and Methods: 21 wistar male rats were placed in 3 groups (healthy, diabetic, aerobic diabetic). Diabetes was induced by peritoneum injection of nicotine amid. Training program lasted 12 weeks, five sessions per week by gradual increase of speed (18 to 26 meters on minutes) and time (10 to 55 minutes) in the form of running on the treadmill. After 12 week aerobic training, PDX-1 and GLUT-2 genes were measured. Data was analyzed using ANOVA with 5 % significance level. Results: Aerobic training caused a significant increase in the expression of GLUT2 (P-value: 0.043) and PDX-1 genes (P-value: 0.007) in the pancreatic tissue of rats with type 2 diabetes (p value: 0.05). Also aerobic training had a significant effect on serum glucose (P-value: 0.001) and insulin levels (P-value: 0.001). Conclusion: It is concluded that aerobic training has significant effects on diabetic control by increasing the expression of PDX1 and GLUT-2 which lowers serum glucose.

4-Methylcatechol stimulates apoptosis and reduces insulin secretion by decreasing betacellulin and inhibin beta-A in INS-1 beta-cells

Insulinoma INS-1 cell line is a pancreatic beta cell tumor which is characterized with high insulin content and secretion in response to increasing glucose levels. 4-Methylcatechol (4-MC) is a metabolite of quercetin, which is known as a potential drug for inhibition of tumorigenesis. The aim of this study was to determine the applying doses of 4-methylcatechol (4-MC) for triggening cell death and decreasing the cell function of rat insulinoma INS-1 beta cells. The rate of apoptosis and the amount of insulin in the cell and the secretions were determined by the ELISA method. Betacellulin (BTC) and inhibin beta-A amounts in both the cell and the glucose induced secretion were investigated by Western blotting. Furthermore, BTC, Inhibin beta-A, Ins1, Ins2, and GLUT2 gene expression levels were determined by the by the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. We noted a significant decrease in cell viability, while an increase in apoptotic cell death by 4-MC treatment. It caused a decrease in the secretion of BTC, expressions of both BTC and inhibin beta-A. We showed a decrease in the expressions of Ins1 and GLUT2, while there is no alteration in the level of insulin protein. Insulin secretion levels increased in INS-1 cells given 4-MC by basal glucose concentration while they did not response to high concentration of glucose, which indicates that 4-MC disrupts the functionality of INS-1 cells. These results revealed that 4-MC induces apoptosis and decreases insulin secretion by reducing BTC and inhibin beta-A in insulinoma INS-1 cells. Thus, 4-MC may be offered as a potential molecule for treatment of insulinoma.

GLUT2-Mediated Glucose Uptake and Availability Are Required for Embryonic Brain Development in Zebrafish

Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 ( glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.