The mechanism of canonical Wnt signaling pathway in type 2 diabetes mice peripheral neuropathy

Abstract

Objective The aim of this study is to explore the mechanism of canonical Wnt signaling pathway in type 2 diabetes mice peripheral neuropathy. Methods Male C57BL6 mice were randomly assigned to three groups. One group treated with normal diet as control. And the rest were used to establish the diabetic model through the combination of 60 kcal% high fat diet and an administration of multipleand low dose of streptozotocin on 5 consecutive days. When the model of type 2 diabetes mice peripheral neuropathy was successfully established, one group was injected with the canonical Wnt signaling pathway inhibitor XAV 939 (T2DM-XAV 939 group) and the other one was injected with phosphate buffer saline (PBS) as control (T2DM-PBS group). The 21st week was the end point of the experiment, and fasting blood glucose, insulin level, homeostasis model assessment for insulin resistance (HOMA-IR), plantar test, and exercise tolerance were measured, realtime PCR were adopted to detect the related mRNA expression of the canonical Wnt signaling pathway. Results T2DM-XAV 939 group had higher total cholesterol, triglyceride, fasting blood glucose, and HOMA-IR than T2DM-PBS group, but showed no statistical difference. The enzymatic activity of glutamic oxaloacetic transaminase was lower level than that in T2DM-PBS group (P<0.05); T2DM-XAV 939 group had significantly higher plantar test and poorer exercise tolerance than those in T2DM-PBS group (P<0.05). The mRNA levels of genes in canonical Wnt signaling pathway such as β-catenin, c-myc, mitochondrial transcription factor A (TFAM) had slightly lower level than those in T2DM-PBS group, without statistical difference, and the protein expression of c-myc was lower than that of T2DM-PBS group (P<0.05). The insulin receptor substeate 2 (IRS-2) mRNA expression was higher than that in T2DM-PBS group (P<0.05). With the development of the experiment, we found that the survival rate of the T2DM-XAV 939 group was significantly reduced compared with the other groups. Conclusion Inhibition of the canonical Wnt signaling pathway may aggravate diabetic peripheral neuropathy. (Chin J Endocrinol Metab, 2018, 34: 1023-1029) Key words: Diabetes mellitus, type 2; Diabetic peripheral neuropathy; Canonical Wnt signaling pathway