1,25(OH)2D3 inhibits pancreatic stellate cells activation and promotes insulin secretion in T2DM.
Endocrine
; 85(3): 1193-1205, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38656750
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 ß 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 ß-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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcitriol
/
Diabetes Mellitus, Experimental
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Diabetes Mellitus, Type 2
/
Pancreatic Stellate Cells
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Insulin Secretion
/
Insulin
Limits:
Animals
Language:
En
Journal:
Endocrine
Journal subject:
ENDOCRINOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China