Glucose-induced release of nitric oxide from mouse pancreatic islets as detected with nitric oxide-selective glass microelectrodes.
Nitric oxide (NO) is believed to play an important role in pancreatic islet physiology and pathophysiology. Research in this area has been hampered, however, by the use of indirect methods to measure islet NO. To investigate the role of NO in islet function, we positioned NO-sensitive, recessed-tip microelectrodes in close proximity to individual islets and monitored oxidation current to detect subnanomolar NO in the bath. NO release from islets consisted of a series of rapid bursts lasting several seconds and/or slow oscillations with a period of approximately 100-300 s. Average baseline NO near the islets in 2.8 mM glucose was 524+/-59 nM (n=12). Raising glucose from 2.8 to 11.1 mM augmented NO release by 429+/-133 nM (n=12, P<0.05), an effect blocked by the NO synthase inhibitor L-NAME (n=3). We also observed that glucose-stimulated increases in NO release were contemporaneous with changes in NAD(P)H and O2 but occurred well before increases in calcium associated with glucose-stimulated insulin secretion. In summary, we demonstrate that NO release from islets is oscillatory and rapidly augmented by glucose, suggesting that NO release occurs early following an increase in glucose metabolism and may contribute to the stimulated insulin secretion triggered by suprathreshold glucose.
Nunemaker
Craig S
CS
University of Virginia Health Sciences, Department of Internal Medicine, Charlottesville, VA 23298, USA.
Buerk
Donald G
DG
Zhang
Min
M
Satin
Leslie S
LS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D019411:Clinical Laboratory Techniques / Q000295:instrumentation*; D004305:Dose-Response Relationship, Drug; D005898:Glass; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008839:Microelectrodes; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D009924:Organ Culture Techniques; D011673:Pulsatile Flow
D009569:Nitric Oxide; D005947:Glucose; D002118:Calcium