Glipizide blocks renal interstitial fibrosis by inhibiting AKT signaling pathway

G. Yang, G. Zeng, J.-P. Wu, O. Jiang, Y.-B. Zeng, S.-J. Huang, J.-J. Huang, D.-Q. Wu

Clinical Laboratory, Affiliated Second People’s Hospital of Luzhou Medical College, Neijiang City, Sichuan, China. daoquanwuzxcc@sina.com

---

• Pharmacology

OBJECTIVE: Diabetes affects the renal function at a certain stage. Oral medication glipizide plays a hypoglycemic effect mainly through releasing insulin, while more insulin is derived from islet β cells. It is still controversy whether antidiabetics. This study mainly intends to investigate the role of glipizide in inhibiting renal interstitial fibrosis.

MATERIALS AND METHODS: A total of 93 SD rats were purchased from Guangdong animal monitoring and established unilateral ureteral obstruction (UUO) model to simulate renal interstitial fibrosis. Forty rats in the experimental group received glipizide intraperitoneal injection for a week at 30 days after modeling, while another 40 rats in the control group received a normal saline injection. The last 10 rats were treated as blank group. Hematoxylin and eosin (HE) staining was applied to test renal interstitial fibrosis. Immunohistochemistry was used to detect fibronectin expression in glomerular and renal tubules. AKT signaling pathway related factors expression was measured by Western blot to determine AKT signal activation.

RESULTS: HE staining showed that the entire kidney cytoplasm red dye becomes shallow, renal medulla gradually disappears, renal tubular epithelial cells enlarge, vacuoles degeneration, renal tubule and collecting tube expansion, inflammatory cells infiltration after UUO modeling. Glipizide treatment decreased dilated renal tubule number, improved glomerulus integrity, and reduced inflammatory infiltration. Fibronectin level in the experimental group was significantly lower than that in control (p<0.05). Western blot revealed that p-AKT expression downregulated after glipizide treatment.

CONCLUSIONS: Glipizide blocks renal interstitial fibrosis by inhibiting AKT signaling pathway.

Free PDF Download