Relationship between metabolic remodeling of pancreatic β-cells and pancreatic histology in type 2 diabetes
Authors' conclusion
PFKFB3-mediated metabolic remodeling occurs in the β-cells of individuals with T2D, and is linked not only to β-cell overload, but to pancreatic fibrosis and local TGF-β/Smad signaling.
Study context
- Population
- Pancreatic sections from deceased individuals with and without T2D; caerulein-treated mice and INS-1,832/13 cells co-cultured with pancreatic stellate cells (PSCs) as fibrosis models
- Participants
- 18 vs 18
- Comparison
- T2D vs no T2D
- T2Dn = 18
- Without T2Dn = 18reference
- Outcome
- Proportion of PFKFB3-positive β-cells
Methodological detailshuman autopsy pancreatic sections, caerulein-treated mouse fibrosis model, INS-1 832/13 cell co-culture with pancreatic stellate cells
- Human autopsy pancreatic sections
- Caerulein-treated mouse fibrosis model
- INS-1 832/13 cell co-culture with pancreatic stellate cells
Main finding
As reported in the abstract
P < 0.05
- PFKFB3 expression negatively correlated with β-cell mass (ρ)
- −0.34
- Amyloid deposition correlated with PFKFB3-positive β-cells (ρ)
- 0.50
- Area of fibrosis correlated with PFKFB3-positive β-cells (ρ)
- 0.84
Further findings
| Outcome | Fibrosis model | Controls | P value |
|---|---|---|---|
| β-cell PFKFB3 positivity in mice, fibrosis model vs controls | 20.5% ± 10.5% | 5.6% ± 5.1% | P < 0.05 |
INS-1 cells co-cultured with PSCs
- Pfkfb3 expression significantly higher after co-culture with PSCs
- RNA sequencing identified transforming growth factor (TGF)-β-related gene clusters; ELISA confirmed high TGF-β levels; western blotting showed greater Smad phosphorylation
Original publication
Relationship between metabolic remodeling of pancreatic β-cells and pancreatic histology in type 2 diabetes. J Clin Endocrinol Metab. Published 5 August 2026. doi:10.
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