Abstract
The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed a systematic analysis of well-preserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20) or type 2 diabetes (T2D) (n = 25) and donors with no diabetes (ND; n = 74). Among ND donors, we found that the incidence of acinar-to-ductal metaplasia (ADM), angiopathy, and pancreatic adiposity increased with age, and ADM and adiposity incidence also increased with BMI. Compared with age-and sex-matched ND organs, T1D pancreata had greater rates of acinar atrophy and angiopathy, with fewer intralobular adipocytes. T2D pancreata had greater rates of ADM and angiopathy and a higher total number of T lymphocytes, but no difference in adipocyte number, compared with ND organs. Although total pancreatic fibrosis was increased in both T1D and T2D, the patterns were different, with peri-ductal and perivascular fibrosis occurring more frequently in T1D pancreata and lobular and parenchymal fibrosis occurring more frequently in T2D. Thus, the exocrine pancreas undergoes distinct changes as individuals age or develop T1D or T2D.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1140-1152 |
| Number of pages | 13 |
| Journal | Diabetes |
| Volume | 73 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2024 |
Funding
This work was supported by the Human Islet Research Network (Research Resource Identifier [RRID] SCR_014393); HPAP (RRID: SCR_016202); grants DK106755, DK123716, DK123743, DK120456, DK104211, DK108120, DK112232, DK112217, DK123594, DK133691, DK117147, T32DK007061, and DK20593 from the National Institute of Diabetes and Digestive and Kidney Diseases and EY032442 from the National Eye Institute (to the Vanderbilt Diabetes Research and Training Center); and the Leona M. and Harry B. Helmsley Charitable Trust, JDRF, the Doris Duke Charitable Foundation, and the Center for Integrated Healthcare, U.S. Department of Veterans Affairs (grant BX000666). This research was performed with the support of nPOD (RRID: SCR_014641), a collaborative T1D research project supported by JDRF (nPOD: 5-SRA-2018-557-Q-R), and the Leona M. and Harry B. Helmsley Charitable Trust (grants 2018PG-T1D053 and G-2108-04793). Acknowledgments. The authors thank the organ donors and their families for their invaluable donations. They also thank investigators from HPAP and nPOD, the International Institute for the Advancement of Medicine, the National Disease Research Exchange, and local organ procurement organizations for their partnership in obtaining these human pancreatic tissues or sections for research. Funding. This work was supported by the Human Islet Research Network (Research Resource Identifier [RRID] SCR_014393); HPAP (RRID: SCR_016202); grants DK106755, DK123716, DK123743, DK120456, DK104211, DK108120, DK112232, DK112217, DK123594, DK133691, DK117147, T32DK007061, and DK20593 from the National Institute of Diabetes and Digestive and Kidney Diseases and EY032442 from the National Eye Institute (to the Vanderbilt Diabetes Research and Training Center); and the Leona M. and Harry B. Helmsley Charitable Trust, JDRF, the Doris Duke Charitable Foundation, and the Center for Integrated Healthcare, U.S. Department of Veterans Affairs (grant BX000666). This research was performed with the support of nPOD (RRID: SCR_014641), a collaborative T1D research project supported by JDRF (nPOD: 5-SRA-2018-557-Q-R), and the Leona M. and Harry B. Helmsley Charitable Trust (grants 2018PG-T1D053 and G-2108-04793).
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
