Role of ATP and Pi in the mechanism of insulin secretion in the mouse insulinoma betaTC3 cell line.

Understanding the biochemical events associated with glucose-stimulated insulin secretion by pancreatic beta 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 betaTC3 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 betaTC3 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 beta cell biochemistry and the mechanism of the 'Fuel Hypothesis' are discussed.