Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells

Endocrinology. 2016 Jan;157(1):166-75. doi: 10.1210/en.2015-1175. Epub 2015 Oct 27.

Abstract

A key question in diabetes research is whether new β-cells can be derived from endogenous, nonendocrine cells. The potential for pancreatic ductal cells to convert into β-cells is a highly debated issue. To date, it remains unclear what anatomical process would result in duct-derived cells coming to exist within preexisting islets. We used a whole-mount technique to directly visualize the pancreatic ductal network in young wild-type mice, young humans, and wild-type and transgenic mice after partial pancreatectomy. Pancreatic ductal networks, originating from the main ductal tree, were found to reside deep within islets in young mice and humans but not in mature mice or humans. These networks were also not present in normal adult mice after partial pancreatectomy, but TGF-β receptor mutant mice demonstrated formation of these intraislet duct structures after partial pancreatectomy. Genetic and viral lineage tracings were used to determine whether endocrine cells were derived from pancreatic ducts. Lineage tracing confirmed that pancreatic ductal cells can typically convert into new β-cells in normal young developing mice as well as in adult TGF-β signaling mutant mice after partial pancreatectomy. Here the direct visual evidence of ducts growing into islets, along with lineage tracing, not only represents strong evidence for duct cells giving rise to β-cells in the postnatal pancreas but also importantly implicates TGF-β signaling in this process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Animals
  • Cadaver
  • Cell Transdifferentiation*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Insulin / biosynthesis*
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / physiology
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / growth & development
  • Islets of Langerhans / physiology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Pancreatectomy
  • Pancreatic Ducts / cytology*
  • Pancreatic Ducts / growth & development
  • Pancreatic Ducts / physiology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Red Fluorescent Protein
  • Regeneration

Substances

  • Insulin
  • Luminescent Proteins
  • Mutant Proteins
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II