Role of ATP and Pi in the mechanism of insulin secretion in the mouse insulinoma βTC3 cell line

Klearchos K. Papas, Robert C. Long, Ioannis Constantinidis, Athanassios Sambanis

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Understanding the biochemical events associated with glucose-stimulated insulin secretion by pancreatic β cells is of importance in gaining insight into both the pathophysiology of diabetes and the development of tissue-engineered bioartificial pancreatic substitutes. We have investigated the effects of glucose concentration on the bioenergetic status and on the metabolic and secretory functions exhibited by mouse insulinoma βTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate (APA) beads. Cells entrapped in APA beads constitute a possible implantable bioartificial pancreas for the long-term treatment of insulin-dependent diabetes mellitus. Our results show that, in entrapped βTC3 cells, the oxygen consumption rate and the intracellular nucleotide triphosphate levels are unaffected by a step change in glucose concentration from 16 mM to 0 mM for 4.5 h and then back to 16 mM. The intracellular Pi level and the ammonia production rate were doubled, while insulin secretion was decreased 10-fold, upon switching from 16 mM to 0 mM glucose. The implications of these findings in the context of pancreatic β cell biochemistry and the mechanism of the 'Fuel Hypothesis' are discussed.

Original languageEnglish (US)
Pages (from-to)807-814
Number of pages8
JournalBiochemical Journal
Volume326
Issue number3
DOIs
StatePublished - Sep 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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