1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM

Zhengyu Zhou; Lewen Zhang; Xun Wei; Aiqing Wang; Yudie Hu; Min Xiao; Yuxuan Zheng

doi:10.1007/s12020-024-03833-0

1,25(OH)₂D₃ inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM

Endocrine. 2024 Apr 24. doi: 10.1007/s12020-024-03833-0. Online ahead of print.

Authors

Zhengyu Zhou¹, Lewen Zhang^#², Xun Wei^#³, Aiqing Wang^#⁴, Yudie Hu², Min Xiao², Yuxuan Zheng²

Affiliations

¹ Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China. zacharyzhou@suda.edu.cn.
² Laboratory Animal Center of Suzhou Medical college, Soochow University, Suzhou, China.
³ Center of Laboratory Animal, Shanghai Jiao Tong University, Shanghai, China.
⁴ Suzhou Medical college of Soochow University, Suzhou, China.

^# Contributed equally.

PMID: 38656750
DOI: 10.1007/s12020-024-03833-0

Abstract

Purpose: To evaluate the effect and mechanism of 1,25(OH)₂D₃ on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM).

Methods: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)₂D₃ for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining. Mouse PSCs were extracted, co-cultured with mouse insulinoma β cells (MIN6 cells) and treated with 1,25(OH)₂D₃. ELISA detection of inflammatory factor expression. Tissue reactive oxygen species (ROS) levels were also measured. Immunofluorescence or Western blotting were used to measure fibrosis and inflammation-related protein expression.

Results: PSCs activation and islets fibrosis in T2DM mice. Elevated blood glucose was accompanied by significant increases in serum inflammatory cytokines and tissue ROS levels. 1,25(OH)₂D₃ attenuated islet fibrosis by reducing hyperglycemia, ROS levels, and inflammatory factors expression. Additionally, the co-culture system confirmed that 1,25(OH)₂D₃ inhibited PSCs activation, reduced the secretion of pro-inflammatory cytokines, down-regulated the expression of fibrosis and inflammation-related proteins, and promoted insulin secretion.

Conclusion: Our findings identify that PSCs activation contributes to islet fibrosis and β-cell dysfunction. 1,25(OH)₂D₃ exerts beneficial effects on T2DM potentially by inhibiting PSCs activation and inflammatory response, highlighting promising control strategies of T2DM by vitamin D.

Keywords: Fibrosis; Inflammation.; Pancreatic stellate cells; Type 2 diabetes mellitus; Vitamin D.

Abstract

Grants and funding