Severely fibrotic pancreases from young patients with chronic pancreatitis

Evidence for a ductal origin of islet neogenesis

S. M. Soltani, T. D. O'Brien, G. Loganathan, M. D. Bellin, T. Anazawa, M. Tiwari, Klearchos K Papas, S. M. Vickers, V. Kumaravel, B. J. Hering, D. E R Sutherland, A. N. Balamurugan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

While it is known that islet cell mass increases considerably after birth, general uncertainty surrounds the source of new beta cells in humans. Chronic pancreatitis (CP) presents a natural injury model for studying postnatal beta-cell regeneration in the human pancreas. In this report, we present histological evidence from human CP pancreases to support the theory that islet neogenesis can occur from ductal precursor cells after birth. Three young patients (ages 16, 12, and 28 years) underwent total pancreatectomy for the management of CP followed by islet isolation and autologous transplantation to prevent or minimize postsurgical diabetes. In all cases, the pancreases had extensive fibrosis, a rock-like consistency, and calcifications in the ducts. During islet isolations, we observed the unusual release of islets with many ductal fragments. In histopathological evaluation of these pancreases, solid cords of cells sometimes formed islet like structures intraductally or extending from ductal structures. Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon, and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both β-cells and α-cells. Labeling for Ki67 to demonstrate mitotic activity showed frequent labeling of duct epithelial cells and of some periductal cells. Using insulin and wide-spectrum cytokeratin double immunofluorescent labeling, we found insulin-positive cells to be present within the ductal lumens, among the cytokeratin-positive ductal epithelium, and extending from the ductal epithelium into surrounding connective tissues, providing evidence for a ductal origin of islet neogenesis.

Original languageEnglish (US)
Pages (from-to)807-814
Number of pages8
JournalActa Diabetologica
Volume50
Issue number5
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Chronic Pancreatitis
Pancreas
Keratins
Chromogranins
Insulin
Epithelium
Parturition
Proinsulin
Islets of Langerhans Transplantation
Pancreatectomy
Endocrine Cells
Autologous Transplantation
Glucagon
Islets of Langerhans
Connective Tissue
Uncertainty
Fluorescent Antibody Technique
Regeneration
Fibrosis
Epithelial Cells

Keywords

  • Beta cell
  • Chronic pancreatitis
  • Islet neogenesis
  • Islet precursor cell
  • Islet progenitor cell

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Soltani, S. M., O'Brien, T. D., Loganathan, G., Bellin, M. D., Anazawa, T., Tiwari, M., ... Balamurugan, A. N. (2013). Severely fibrotic pancreases from young patients with chronic pancreatitis: Evidence for a ductal origin of islet neogenesis. Acta Diabetologica, 50(5), 807-814. https://doi.org/10.1007/s00592-011-0306-9

Severely fibrotic pancreases from young patients with chronic pancreatitis : Evidence for a ductal origin of islet neogenesis. / Soltani, S. M.; O'Brien, T. D.; Loganathan, G.; Bellin, M. D.; Anazawa, T.; Tiwari, M.; Papas, Klearchos K; Vickers, S. M.; Kumaravel, V.; Hering, B. J.; Sutherland, D. E R; Balamurugan, A. N.

In: Acta Diabetologica, Vol. 50, No. 5, 2013, p. 807-814.

Research output: Contribution to journalArticle

Soltani, SM, O'Brien, TD, Loganathan, G, Bellin, MD, Anazawa, T, Tiwari, M, Papas, KK, Vickers, SM, Kumaravel, V, Hering, BJ, Sutherland, DER & Balamurugan, AN 2013, 'Severely fibrotic pancreases from young patients with chronic pancreatitis: Evidence for a ductal origin of islet neogenesis', Acta Diabetologica, vol. 50, no. 5, pp. 807-814. https://doi.org/10.1007/s00592-011-0306-9
Soltani, S. M. ; O'Brien, T. D. ; Loganathan, G. ; Bellin, M. D. ; Anazawa, T. ; Tiwari, M. ; Papas, Klearchos K ; Vickers, S. M. ; Kumaravel, V. ; Hering, B. J. ; Sutherland, D. E R ; Balamurugan, A. N. / Severely fibrotic pancreases from young patients with chronic pancreatitis : Evidence for a ductal origin of islet neogenesis. In: Acta Diabetologica. 2013 ; Vol. 50, No. 5. pp. 807-814.
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