The succinoglycan riclin restores beta cell function through the regulation of macrophages on Th1 and Th2 differentiation in type 1 diabetic mice.

Zhao Ding, Rui Cheng, Yunxia Yang, Yang Zhao, Wenhao Ge, Xiaqing Sun, Xi Xu, Shiming Wang, Jianfa Zhang

Food & function 2021 Nov 15

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Bacterial succinoglycan is found suitable as a viscosifying and emulsifying agent in the food industry. Riclin is a de-succinyl succinoglycan from an Agrobacterium isolate. Our previous study has revealed that riclin exerts special anti-inflammatory effects in vitro and in vivo. This study aims to determine the effects of riclin on preventing against immunological injury of beta cells in a type 1 diabetic model. We found that orally riclin effectively restores beta-cell function and improves the complications of streptozotocin (STZ)-induced diabetes. Riclin also reduces STZ-induced liver and kidney damage, and balances the inappropriate ratio of T helper type 1 cell (Th1)/type 2 cell (Th2) in the spleen and pancreatic draining lymph nodes of the STZ-induced diabetic mice. In a co-culture system with the islet β cell MIN6 and macrophage RAW 264.7, riclin reduces the levels of IFN-γ and IL-1β, protecting against STZ-caused MIN6 cell injury. We identified that riclin specifically binds to the membrane of macrophages and regulates the ratio of IL-10 and IL-12, thereby inhibiting the macrophage-mediated polarization of Th1 cells and promoting the differentiation of Th2 cells, which depends on the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor. Moreover, orally riclin significantly decreases the incidence of STZ-induced hyperglycemia (7.1% in riclin vs. 92.9% in STZ), and prevents autoimmune diabetes in non-obese diabetic (NOD) mice, with 87.5% of mice free of diabetes compared to 46.6% of the control mice. These results suggest that riclin has potential to be a functional food to prevent and improve autoimmune diabetes and related diseases.

Citation

Zhao Ding, Rui Cheng, Yunxia Yang, Yang Zhao, Wenhao Ge, Xiaqing Sun, Xi Xu, Shiming Wang, Jianfa Zhang. The succinoglycan riclin restores beta cell function through the regulation of macrophages on Th1 and Th2 differentiation in type 1 diabetic mice. Food & function. 2021 Nov 15;12(22):11611-11624