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

Doliba NM, Qin W, Vatamaniuk MZ, Buettger CW, Collins HW, Magnuson MA, Kaestner KH, Wilson DF, Carr RD, Matschinsky FM
Am J Physiol Endocrinol Metab. 2006 291 (3): E525-35

PMID: 16638820 · DOI:10.1152/ajpendo.00579.2005

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 Ca(2+), insulin, and glucagon secretion. By use of a method based on O(2) quenching of phosphorescence, the O(2) 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 microM) 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 Ca(2+) 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.

MeSH Terms (27)

Acetylcholine Acetylcholinesterase Amino Acids Animals ATP-Binding Cassette Transporters Calcium Cell Respiration Cholinergic Fibers Gene Expression Glucagon Glucose Glucose Transporter Type 2 Glyburide Hormones Insulin Insulin Secretion Islets of Langerhans Large-Conductance Calcium-Activated Potassium Channel beta Subunits Mice Mice, Inbred C57BL Mice, Knockout Multidrug Resistance-Associated Proteins Oxygen Consumption Potassium Channels, Inwardly Rectifying Receptors, Drug RNA, Messenger Sulfonylurea Receptors

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