Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: Potential role of NTPDase3 in insulin secretion

Elise G. Lavoie, Michel Fausther, Gilles Kauffenstein, Filip Kukulski, Beat M. Künzli, Helmut Friess, Jean Sévigny

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Extracellular nucleotides and adenosine regulate endocrine pancreatic functions such as insulin secretion by Langerhans islet β-cells via the activation of specific P2 and P1 receptors. Membrane-bound ectonucleotidases regulate the local concentration of these ligands and consequently control the activation of their receptors. The objective of this study was to identify and localize the major ectonucleotidases, namely NTPDases and ecto-5′- nucleotidase, present in the endocrine pancreas. In addition, the potential implication of ecto-ATPase activity on insulin secretion was investigated in the rat β-cell line INS-1 (832/13). The localization of ectonucleotidase activity and protein was carried out in situ by enzyme histochemistry and immunolocalization in mouse, rat, and human pancreas sections. NTPDase1 was localized in all blood vessels and acini, and NTPDase2 was localized in capillaries of Langerhans islets and in peripheral conjunctive tissue, whereas NTPDase3 was detected in all Langerhans islet cell types. Interestingly, among the mammalian species tested, ecto-5′-nucleotidase was present only in rat Langerhans islet cells, where it was coexpressed with NTPDase3. Notably, the inhibition of NTPDase3 activity by BG0136 and NF279 facilitated insulin release from INS-1 (832/13) cells under conditions of low glycemia, probably by affecting P2 receptor activation. NTPDase3 activity also regulated the inhibitory effect of exogenous ATP in the presence of a high glucose concentration most likely by controlling adenosine production. In conclusion, all pancreatic endocrine cells express NTPDase3 that was shown to modulate insulin secretion in rat INS-1 (832/13) β-cells. Ecto-5′-nucleotidase is expressed in rat Langerhans islet cells but absent in human and mouse endocrine cells.

Original languageEnglish
Pages (from-to)E647-E656
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume299
Issue number4
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Ecto-5′-nucleotidase/CD73
  • INS-1 (832/13)
  • Nucleoside triphosphate diphosphohydrolase
  • P2 receptors
  • Purinergic signaling

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