Mitochondrial priming modifies Ca2+ oscillations and insulin secretion in pancreatic islets.
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.
Ainscow
E K
EK
Department of Biochemistry, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, U.K.
Rutter
G A
GA
D000255:Adenosine Triphosphate / Q000032:analysis / Q000096:biosynthesis; D000331:Aequorin / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D000331:Aequorin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D008156:Luciferases; D005947:Glucose; D002118:Calcium