Intrapancreatic adipocytes and beta cell dedifferentiation in human type 2 diabetes
Authors' conclusion
Higher pancreatic fat content was accompanied by increased beta cell dedifferentiation in the individuals with diabetes. Clusters of adipocytes significantly contribute to higher pancreatic fat content and immune cell recruitment. Overall, the interactions among adipocytes, immune cells and beta cells in the pancreas microenvironment might contribute to beta cell failure and dedifferentiation in type 2 diabetes.
Study context
- Population
- Human pancreatic specimens from organ donors; scRNA-seq of 11 T2D donors from the Human Pancreatic Analysis Project database
- Participants
- 50 organ donors
- Comparison
- T2D vs non-diabetic organ donors; higher vs lower pancreatic fat content in T2D
- T2Dn = 15
- Without T2Dn = 35reference
- Outcome
- Pancreatic fat content
Methodological detailshistological analysis of organ-donor pancreases, single-cell RNA-seq bioinformatic analysis
- Histological analysis of organ-donor pancreases
- Single-cell RNA-seq bioinformatic analysis
Main finding
As reported in the abstract
P < 0.001
- Correlation of pancreatic fat content with estimated beta cell mass
- r=−0.675, p=0.006
- Correlation of pancreatic fat content with alpha-to-beta cell ratio
- r=0.608, p=0.016
Further findings
scRNA-seq in T2D donors with higher pancreatic fat content
- ALDH1A3 (dedifferentiation marker) expression significantly increased in alpha and beta cells; NPY decreased in beta cells
- Pseudotime: beta cell dedifferentiation and transdifferentiation towards alpha cells, with decreased INSM1, MafA and NPY; inflammation and immune response pathways activated
Histological ALDH1A3 positivity vs pancreatic fat content
- Correlation with % ALDH1A3+ beta cells within islets
- r=0.594, p=0.020
- Correlation with ALDH1A3 positivity rate in beta cells
- r=0.615, p=0.015
- T cells adjacent to adipocytes related to adipocyte distribution pattern and islet dedifferentiation phenotype
Original publication
Intrapancreatic adipocytes and beta cell dedifferentiation in human type 2 diabetes. Diabetologia. Published 12 March 2025. doi:10.
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