aThe characteristics of glucose metabolism in the sulfonylurea receptor 1 knockout rat model

Abstract

Abstract Background Sulfonylurea receptor 1 (SUR1) is primarily responsible for glucose regulation in normal conditions. Here, we sought to investigate the glucose metabolism characteristics of SUR1 −/− rats. Methods The TALEN technique was used to construct a SUR1 gene deficiency rat model. Rats were grouped by SUR1 gene knockout or not and sex difference. Body weight; glucose metabolism indicators, including IPGTT, IPITT, glycogen contents and so on; and other molecule changes were examined. Results Insulin secretion was significantly inhibited by knocking out the SUR1 gene. SUR1 −/− rats showed lower body weights compared to wild-type rats, and even SUR1 −/− males weighed less than wild-type females. Upon SUR1 gene knockout, the rats showed a peculiar plasma glucose profile. During IPGTT, plasma glucose levels were significantly elevated in SUR1 −/− rats at 15 min, which could be explained by SUR1 mainly working in the first phase of insulin secretion. Moreover, SUR1 −/− male rats showed obviously impaired glucose tolerance than before and a better insulin sensitivity in the 12th week compared with females, which might be related with excess androgen secretion in adulthood. Increased glycogen content and GLUT4 expression and the inactivation of GSK3 were also observed in SUR1 −/− rats, which suggested an enhancement of insulin sensitivity. Conclusions These results reconfirm the role of SUR1 in systemic glucose metabolism. More importantly, our SUR1 −/− rat model might be applied in other fields, such as for exploring other hypoglycaemic functions of sulfonylureas.

Keywords

• Sulfonylurea receptor 1
• Knockout rat model
• Glucose metabolism
• Insulin sensitivity