Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model

Abstract

In recent years, the incidence of type 1 diabetes mellitus (T1DM) has been increasing. The role of CXCL10 and its receptor, CXCR3, in the occurrence of T1DM has drawn lots of research interests, as the disease incidence was correlated with their expression levels. We thus used an antagonist of CXCR3, NBI-74330, to block the specific binding, for further observation of islet cell apoptosis in a T1MD rat model. A total of 80 SD rats were given STZ intraperitoneally for generating T1DM model. Different concentrations of NBI-74330 were then applied, followed by the collection of blood and pancreatic tissue samples. CXCL10 and CXCR3 levels were detected by enzyme linked immunosorbent assay (ELISA), followed by expressional assays in pancreatic tissues by real-time PCR, Western blotting and flow cytometry. Compared to control group, model rats had significantly elevated blood glucose level (>16.7 mmol/L), with depressed CXCL10 and CXCR3 levels compared to model group (P<0.05). After NBI-74330 treatment, mRNA and protein levels of CXCL10 and CXCR3 were significantly lowered, with significantly decreased apoptotic cell ratios compared to model group (P<0.05). CXCL10 receptor antagonist NBI-74330 can inhibit the apoptosis of pancreatic islet cells in T1DM rats.

Keywords: CXCL10; CXCR3; NBI-74330; Type 1 diabetes mellitus.

Figure 1

CXCL10 (A) and CXCR3 (B) expression level in serum. *P<0.05 compared to control group.

Figure 2

CXCL10 (A) and CXCR3 (B) mRNA levels. *P<0.05 compared to control group.

Figure 3

CXCL10 (B) and CXCR3 (C) protein levels in pancreatic tissues of rats. (A) representative protein bands. *P<0.05 compared to control group.

Figure 4

Effect of NBI-74330 on apoptosis of pancreatic tissues. (A) Control; (B) Low-dosage drugs; (C) Moderate-dosage drugs; (D) High-dosage drugs. Right panel, quantitative analysis of (A) to (D). *P<0.05 compared to control group.