Single pancreatic beta cells co-express multiple islet hormone genes in mice

Hitoshi Katsuta, T. Akashi, R. Katsuta, M. Nagaya, D. Kim, Yojiro Arinobu, M. Hara, S. Bonner-Weir, A. J. Sharma, Koichi Akashi, G. C. Weir

Research output: Contribution to journalArticle

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Abstract

Aims/hypothesis: It is widely accepted that production of insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells is specific to beta, alpha, delta and pancreatic polypeptide cells, respectively. We examined whether beta cells express other genes encoding islet hormones. Methods: Nested RT-PCR was performed on single beta cells of transgenic mice with green fluorescent protein (GFP) driven by mouse insulin I promoter (MIP-GFP). Results: Only 55% of adult beta cells expressed the insulin gene alone, while others expressed two or more islet hormone genes; 4% expressed all four hormone genes. In embryonic and neonatal cells, 60% to 80% of GFP+ cells co-expressed pancreatic polypeptide and insulin genes in contrast to 29% in adult. To clarify cell fate, we conducted lineage tracing using rat insulin II promoter-cre mice crossed with reporter mice Gt(ROSA)26Sor-loxP-flanked STOP-cassette-GFP. All GFP+ cells expressed insulin I and II genes, and showed similar heterogeneity of co-expression to that seen in MIP-GFP mice. Although we report expression of other hormone genes in a significant proportion of beta cells, our lineage tracing results demonstrate that after inducing InsII (also known as Ins2) expression, beta cell progenitors do not redifferentiate to non-beta cells. Conclusions/interpretation: This study shows co-expression of multiple hormone genes in beta cells of adult mice as well as in embryos and neonates. This finding could: (1) represent residual expression from beta cell precursors; (2) result from alternative developmental pathways for beta cells; or (3) denote the differentiation potential of these cells. It may be linked to functional heterogeneity. This heterogeneity in gene expression may provide a means to characterise the functional, cellular and developmental heterogeneity seen in beta cells.

Original languageEnglish
Pages (from-to)128-138
Number of pages11
JournalDiabetologia
Volume53
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

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Insulin-Secreting Cells
Hormones
Green Fluorescent Proteins
Genes
Insulin
Pancreatic Polypeptide
Pancreatic Polypeptide-Secreting Cells
Cell Lineage
Somatostatin
Glucagon
Islets of Langerhans
Transgenic Mice
Cell Differentiation
Stem Cells
Embryonic Structures

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Single pancreatic beta cells co-express multiple islet hormone genes in mice. / Katsuta, Hitoshi; Akashi, T.; Katsuta, R.; Nagaya, M.; Kim, D.; Arinobu, Yojiro; Hara, M.; Bonner-Weir, S.; Sharma, A. J.; Akashi, Koichi; Weir, G. C.

In: Diabetologia, Vol. 53, No. 1, 01.01.2010, p. 128-138.

Research output: Contribution to journalArticle

Katsuta, H, Akashi, T, Katsuta, R, Nagaya, M, Kim, D, Arinobu, Y, Hara, M, Bonner-Weir, S, Sharma, AJ, Akashi, K & Weir, GC 2010, 'Single pancreatic beta cells co-express multiple islet hormone genes in mice', Diabetologia, vol. 53, no. 1, pp. 128-138. https://doi.org/10.1007/s00125-009-1570-x
Katsuta, Hitoshi ; Akashi, T. ; Katsuta, R. ; Nagaya, M. ; Kim, D. ; Arinobu, Yojiro ; Hara, M. ; Bonner-Weir, S. ; Sharma, A. J. ; Akashi, Koichi ; Weir, G. C. / Single pancreatic beta cells co-express multiple islet hormone genes in mice. In: Diabetologia. 2010 ; Vol. 53, No. 1. pp. 128-138.
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