Mechanism of interleukin-22 regulating insulin resistance in polycystic ovary syndrome rats
10.3760/cma.j.cn101441-20211201-00533
- VernacularTitle:白细胞介素-22在多囊卵巢综合征大鼠胰岛素抵抗中的作用机制
- Author:
Xiaochen MA
1
;
Yujuan QI
;
Ying LIU
;
Fang SUN
;
Xiaonan YAN
;
Bei ZHANG
Author Information
1. 徐州医科大学徐州临床学院，徐州 221009
- Publication Type:Journal Article
- Keywords:
Polycystic ovary syndrome;
Insulin resistance;
Interleukin-22;
Pancreatic β cells
- From:
Chinese Journal of Reproduction and Contraception
2023;43(2):184-190
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the mechanism of pancreatic interleukin-22 (IL-22) signaling pathway regulating insulin resistance (IR) in polycystic ovary syndrome (PCOS) rats.Methods:Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer. PCOS rats implanted with a silastic tube filled with dihydrotestosterone (DHT) at dosage of 7.5 mg. Their body weight was monitored weekly. At the end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin test (IPITT) were conducted, the serum IL-22 and fasting insulin (FINS) were monitored through the enzyme-linked immunosorbent assay (ELISA), and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The location and differential expression of the interleukin-22 receptor 1 (IL-22R1) in pancreatic β cells were observed by immunofluorescence staining, and the expressions of the IL-22, Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3) proteins were detected by Western blotting.Results:Compared with control group, the body weight was increased [(420.50±10.26) g vs. (314.40±6.54) g, P=0.003] and the serum level of IL-22 in PCOS group was decreased [(9.86±1.41) ng/L vs. (16.07±4.68) ng/L, P=0.038]. The levels of FINS and HOMA-IR were higher in PCOS group than in control group [(17.97±2.86) mU/L vs. (13.05±2.12) mU/L, P=0.001; 4.46±0.80 vs. 2.99±0.61, P=0.001]. The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min, 60 min and 90 min compared with control group [(15.58±1.86) mmol/L vs. (12.54±1.60) mmol/L, P=0.010;(10.71±2.07) mmol/L vs. (8.33±1.02) mmol/L, P=0.026; (7.47±1.36) mmol/L vs. (6.28±0.72) mmol/L, P=0.013], as well as the area under curve (AUC) [(1 248.71±164.23) mmol/(L·min) vs. (1 007.29±102.29) mmol/(L·min), P=0.010]. Following IPITT, compared with control group, PCOS group showed significantly higher 60 min [(3.12±0.28) mmol/L vs. (2.60±0.28) mmol/L, P=0.031], 90 min [(2.62±0.17) mmol/L vs. (2.10±0.33) mmol/L, P=0.026] and 120 min glucose level [(2.28±0.25) mmol/L vs. (1.90±0.24) mmol/L, P=0.033], as well as the AUC [(414.60±23.06) mmol/(L·min) vs. (359.40±39.95) mmol/(L·min), P=0.044]. The immunofluorescence results suggested that IL-22R1 and INS were colocalized in pancreatic β cells and the expression of IL-22R1 was lower in PCOS group than in control group (48.26±3.83 vs. 63.44±2.66, P=0.031). Further, the levels of pancreatic IL-22 and p-STAT3 protein were significantly lower in PCOS group than in control group (0.82±0.09 vs. 1.01±0.06, P=0.025; 0.77±0.09 vs. 1.01±0.07, P=0.015). Conclusion:Our results demonstrated that the abnormality of IL-22 may result in IR through attenuating the activation of STAT3 signaling pathway and decreasing the level of p-STAT3 in the pancreatic tissue of PCOS rats.
