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bioRxiv · 10.1101/2021.10.22.465460

Oral administration of bacterial Beta cell expansion factor A (BefA) alleviates diabetes in mice with Type 1 and Type 2 diabetes

Wang, H.·Wei, J.·Hu, H.·Le, F.·Wu, H.·Wei, H.·Luo, J.·Chen, T.
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Abstract

Diabetes mellitus (DM) is a group of metabolic diseases, which is of urgent need to develop new therapeutic DM oral drugs with less side effects and sound therapeutic efficacy. In this study, a Beta cell expansion factor A (BefA) production strain of Escherichia Coli BL21-pet 28C-BefA was constructed, and the anti-diabetes effect of BefA was evaluated using type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mice models. The T1DM mice results indicated that BefA significantly reduced the blood glucose level, exerted protective function of islet {beta} cell morphology, down-regulated the TLR-4, p-NF{kappa}B/NF{kappa}B, Bax/Bcl-2 expressions and the secretion level of IL-1{beta}, TNF-, increased the expression of PDX-1 protein and insulin secretion in a concentration-dependent manner, and restored the disturbed microbial diversity to normal level. Similar with the T1DM mice, BefA obviously increased islet {beta} cells, reduced inflammatory reaction and apoptosis in T2DM mice, and also improved liver lipid metabolism by down-regulating the expression of CEBP-, ACC, Fasn and inhibiting the synthesis of triglyceride and induce Cpt-1, Hmgcs2, Ppar in a concentration-dependent manner. In the present study, we verified therapeutic effect and potential mechanisms of BefA in mammal for the first time, providing basic data for its clinical application.

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Wang, H., Wei, J., Hu, H., Le, F., Wu, H., Wei, H., Luo, J., Chen, T.. 2021-10-24. Oral administration of bacterial Beta cell expansion factor A (BefA) alleviates diabetes in mice with Type 1 and Type 2 diabetes. https://doi.org/10.1101/2021.10.22.465460

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