Effect of GPR41 deletion on type 1 diabetes and its mechanism

• 1、School of Food Science and Technology, Jiangnan University, WuXi, P.R. China 214122
• 2、School of Medicine, Jiangnan University, WuXi, P.R. China 214122

Abstract：Objective: To investigate the role of GPR41 as a membrane receptor in regulating the pathogenesis and molecular mechanisms of type 1 diabetes (T1D). Methods: T1D model was established by streptozotocin (STZ). Twenty-four 8-week-old SPF C57BL / 6J male mice were randomly divided into normal control group (control group), model group (STZ group), and GPR41 deletion group ( GPR41-/-STZ group). Intraperitoneal injection of 45 mg / kg of STZ for 5 consecutive days. It was observed that mice that measured fasting blood glucose ≥11.1 mmol / dl twice in a row were considered to be diabetic. Roche blood glucose meter was used to measure fasting blood glucose in mice, qPCR was used to determine tumor necrosis factor (TNF) -α, transforming growth factor (TGF) -β, interleukin (IL) -12, IL-23, IL-10 and CD86 in pancreatic tissues; Flow cytometry was used to determine dendritic cells (CD11c + CD11b +), macrophages (M1: CD11b + F4 / 80 + CD11c +, M2: CD11b + F4 / 80 + cd206 +), and effector T cells (IFN-γ +) in the pancreas. CD8 +) and TH1 helper cells (IFN-γ + CD4 +). Western blot was used to detect the expression of cytokine signal inhibitor (SOCS) 1, SOCS3 and signal transduction and transcription activation protein (STAT) 3. Happening. Results: The absence of GPR41 can significantly promote the onset of T1D, which is markedly increased blood glucose, weight loss, increased drinking water, islet atrophy in pancreatic tissue pathology, mature dendritic cells increased, SOCS3 inhibited, and STAT3 phosphorylation increased. Conclusions: Deletion of GPR41 inhibited the expression of SOCS3, promoted the phosphorylation of STAT3, accelerated the maturation of dendritic cells, activated effector T cells, and thus accelerated the onset of T1D.

Keywords： type 1 diabetes GPR41 dendritic cells SOCS3 p-STAT3