Abstract

More and more studies have shown that the intestinal microbiota is the main factor in the pathogenesis of type 1 diabetes mellitus (T1DM). Beta cell expansion factor A (BefA) is a protein expressed by intestinal microorganisms. It has been proven to promote the proliferation of β-cells and has broad application prospects. However, as an intestinal protein, there have not been studies and reports on its application in diabetes and its mechanism of action. In this study, a T1DM model induced by multiple low-dose STZ (MLD-STZ) injections was established, and BefA protein was administered to explore its therapeutic effect in T1DM and the potential mechanism of intestinal microbiota. BefA protein significantly reduced the blood glucose, maintained the body weight, and improved the glucose tolerance of the mice. At the same time, the BefA protein significantly increased the expression of ZO-1, Occludin, and significantly reduced the expression of TLR-4, Myd88, and p-p65/p65. BefA protein significantly reduced the relative expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In addition, our high-throughput sequencing shows for the first time that the good hypoglycemic effect of BefA protein is strongly related to the increase in the abundance of the beneficial gut bacteria Lactobacillus, Bifidobacterium and Oscillospria and the decrease in the abundance of the opportunistic pathogen Acinetobacter. Our group used animal models to verify the hypoglycemic effect of BefA protein, and first explored the potential mechanism of intestinal microbiota in BefA protein treatment.

Highlights

  • Diabetes (Diabetes Mellitus, DM) is a group of metabolic diseases that chronically increase blood glucose levels due to defective insulin secretion or impaired biological effects, and is mainly divided into type 1 diabetes and type 2 diabetes

  • Our results showed that the Beta cell expansion factor A (BefA) protein showed a good hypoglycemic effect from the 14th day, and the 28th day had a more significant hypoglycemic effect compared with the M group (13.84 mmol/L vs 22.52 mmol/L, p < 0.01) (Figure 1B)

  • The GTT results showed that, the BefA protein significantly improved the blood glucose tolerance of the mice compared with the M group

Read more

Summary

Introduction

Diabetes (Diabetes Mellitus, DM) is a group of metabolic diseases that chronically increase blood glucose levels due to defective insulin secretion or impaired biological effects, and is mainly divided into type 1 (insulin-dependent, T1DM) diabetes and type 2 (non-insulin-dependent, T2DM) diabetes. Long-term hyperglycemia in patients with T1DM is a major factor leading to chronic damage and dysfunction of various tissues such as liver, kidney, heart, retina, and cerebrovascular (Dimeglio et al, 2018). Diabetic heart disease, cerebrovascular illness and kidney disease are the main reasons of death, bringing a heavy burden to the patient’s family and social medical system (Deshpande et al, 2008; Núñez et al, 2019)

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call