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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/E525    most recent 00579.2005v2 00579.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Doliba, N. M. Articles by Matschinsky, F. M. Search for Related Content PubMed PubMed Citation Articles by Doliba, N. M. Articles by Matschinsky, F. M.

Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1^–/– mouse islets

¹Department of Biochemistry and Biophysics, ²Institute for Diabetes, Obesity and Metabolism, and ³Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; ⁴Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; and ⁵Pharmacological Research 1, Novo Nordisk, Bagsvaerd, Denmark

Submitted 23 November 2005 ; accepted in final form 13 April 2006

Neural and endocrine factors (i.e., Ach and GLP-1) restore defective glucose-stimulated insulin release in pancreatic islets lacking sulfonylurea type 1 receptors (SUR1^–/–) (Doliba NM, Qin W, Vatamaniuk MZ, Li C, Zelent D, Najafi H, Buettger CW, Collins HW, Carr RD, Magnuson MA, and Matschinsky FM. Am J Physiol Endocrinol Metab 286: E834–E843, 2004). The goal of the present study was to assess fuel-induced respiration in SUR1^–/– islets and to correlate it with changes in intracellular Ca²⁺, insulin, and glucagon secretion. By use of a method based on O₂ quenching of phosphorescence, the O₂ consumption rate (OCR) of isolated islets was measured online in a perifusion system. Basal insulin release (IR) was 7–10 times higher in SUR1^–/– compared with control (CON) islets, but the OCR was comparable. The effect of high glucose (16.7 mM) on IR and OCR was markedly reduced in SUR1^–/– islets compared with CON. Ach (0.5 µM) in the presence of 16.7 mM glucose caused a large burst of IR in CON and SUR1^–/– islets with minor changes in OCR in both groups of islets. In SUR1^–/– islets, high glucose failed to inhibit glucagon secretion during stimulation with amino acids or Ach. We conclude that 1) reduced glucose responsiveness of SUR1^–/– islets may be in part due to impaired energetics, as evidenced by significant decrease in glucose-stimulated OCR; 2) elevated intracellular Ca²⁺ levels may contribute to altered insulin and glucagon secretion in SUR1^–/– islets; and 3) The amplitudes of the changes in OCR during glucose and Ach stimulation do not correlate with IR in normal and SUR1^–/– islets suggesting that the energy requirements for exocytosis are minor compared with other ATP-consuming reactions.

sulfonylurea receptor 1 knockout mice; acetylcholine; insulin and glucagon release; calcium; oxygen consumption

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