Role and mechanism of PI3K/AKT/FoxO1/PDX-1 signaling pathway in functional changes of pancreatic islets in rats after severe burns

LIFE SCIENCES

卷:258

Article

Zhang, Bohan¹  Sun, Pengchao¹  Shen, Chuan'an¹  Liu, Xinzhu¹  Sun, Jiachen¹  Li, Dawei¹  Liu, Zhaoxing¹  Zhang, Wen¹  Zhang, Kun¹  Niu, Yuezeng¹ 

[1] Chinese Peoples Liberat Army Gen Hosp, Dept Burns & Plast Surg, Med Ctr 4, 51 Fucheng Rd, Beijing 100048, Peoples R China

关键词: Burns;    Phosphoinositide 3-kinase (PI3K);    Serine threonine kinase (AKT);    Forkhead box protein O1 (FoxO1);    Pancreatic and duodenal homeobox-1 (PDX-1);    Glucose metabolism;    Hyperglycemia;    Bupivacaine (BPV (HOpic));   

DOI  :  10.1016/j.lfs.2020.118145

来源: Elsevier

【 摘 要 】

Aims: Studies on diabetes mellitus have shown that the phosphoinositide 3-kinase (PI3K)/serine threonine kinase (AKT)/forkhead box protein O1 (FoxO1) signaling pathway can regulate insulin secretion by modulating the expression of pancreatic and duodenal homeobox-1 (PDX-1). Therefore, it was hypothesized that the pathway also played an important role in functional abnormalities of pancreatic islets after severe burns. This study aimed to explore the role and mechanism of the PI3K/AKT/FoxO/PDX-1 signaling pathway in functional changes of pancreatic islets in rats post severe burns. Main methods: Rats were grouped, subjected to full thickness burn injuries involving 50% total body surface area (TBSA), and injected intraperitoneally with BPV (HOpic) (0.6 mg/kg) or DMSO (0.55 mg/kg) once a day for three days. Glucose metabolism related indexes were measured by the glucometer, transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA). PI3K/AKT/FoxO1/PDX-1 signaling pathway related indexes were detected through immunofluorescence, western blot and RT-qPCR analyses. Key findings: Dysglycemia and impaired insulin secretion occurred in rats, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets fell, and PDX-1 was translocated from the nucleus to the cytoplasm post severe burns. When BPV (HOpic) was used, glucose metabolism and insulin secretion were improved, the activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway in the islets was up-regulated, and PDX-1 was redistributed from the cytoplasm to the nucleus. Significance: The activity of the PI3K/AKT/FoxO1/PDX-1 signaling pathway declined following severe burns. When its activity was up-regulated, insulin secretion could be improved, thus ameliorating hyperglycemia.

【 授权许可】

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