Mitochondrial priming modifies Ca2+ oscillations and insulin secretion in pancreatic islets

Biochem J. 2001 Jan 15;353(Pt 2):175-80. doi: 10.1042/0264-6021:3530175.

Abstract

Increases in mitochondrial [Ca(2+)] ([Ca(2+)](m)) have recently been reported to cause long-term alterations in cellular ATP production [Jouaville, Bastianutto, Rutter and Rizzuto (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 13807-13812]. We have determined the importance of this phenomenon for nutrient sensing in pancreatic islets and beta-cells by imaging adenovirally expressed Ca(2+) and ATP sensors (aequorin and firefly luciferase). [Ca(2+)](m) increases provoked by KCl or tolbutamide evoked an immediate increase in cytosolic and mitochondrial free ATP concentration ([ATP](c) and [ATP](m) respectively) at 3 mM glucose. Subsequent increases in [glucose] (to 16 or 30 mM) then caused a substantially larger increase in [ATP](c) and [ATP](m) than in naïve cells, and pre-stimulation with tolbutamide led to a larger secretory response in response to glucose. Whereas pre-challenge of islets with KCl altered the response to high [glucose] of [Ca(2+)](m) from periodic oscillations to a sustained elevation, oscillations in [ATP](c) were observed neither in naïve nor in stimulated islets. Hence, long-term potentiation of mitochondrial ATP synthesis is a central element in nutrient recognition by pancreatic islets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / biosynthesis
  • Aequorin / genetics
  • Animals
  • Calcium / analysis
  • Calcium / metabolism*
  • Cell Line
  • Cells, Cultured
  • Cytomegalovirus / genetics
  • Glucose / metabolism
  • Glucose / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Luciferases / genetics
  • Luminescent Measurements
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Wistar
  • Tolbutamide / pharmacology

Substances

  • Hypoglycemic Agents
  • Insulin
  • Aequorin
  • Potassium Chloride
  • Adenosine Triphosphate
  • Tolbutamide
  • Luciferases
  • Glucose
  • Calcium