title: Glucose decreases extracellular adenosine levels in isolated mouse and rat pancreatic islets.
abstract: The pancreatic islets of Langerhans are responsible for the regulated release of the endocrine hormones insulin and glucagon that participate in the control of glucose homeostasis. Abnormal regulation of these hormones can result in glucose intolerance and lead to the development of diabetes. Numerous efforts have been made to better understand the physiological regulators of insulin and glucagon secretion. One of these regulators is the purine nucleoside, adenosine. Though exogenous application of adenosine has been demonstrated to stimulate glucagon release and inhibit insulin release, the physiological significance of this pathway has been unclear. We used a novel 7 µm enzyme-coated electrode biosensor to measure adenosine levels in isolated rodent islets. In the mouse islets, basal adenosine levels in the presence of 3 mM glucose were estimated to be 5.7 ± 0.6 µM. As glucose was increased, extracellular adenosine diminished. A 10-fold increase of extracellular KCl increased adenosine levels to 16.4 ± 2.0 µM. This release required extracellular Ca (2+) suggesting that it occurred via an exocytosis-dependent mechanism. We also found that while rat islets were able to convert exogenous ATP into adenosine, mouse islets were unable to do this. Our study demonstrates for the first time the basal levels of adenosine and its inverse relationship to extracellular glucose in pancreatic islets.
authors.affiliation: Department of Cellular and Physiological Sciences; University of British Columbia; Vancouver, BC Canada.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Yang
authors.affiliation: School of Life Sciences; University of Warwick; Coventry, West Midlands, UK.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Squires
authors.affiliation: School of Life Sciences; University of Warwick; Coventry, West Midlands, UK; Sarissa Biomedical Ltd.; Coventry, West Midlands, UK.
authors.forename: Faming
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Cellular and Physiological Sciences; University of British Columbia; Vancouver, BC Canada; Department of Surgery; University of British Columbia; Vancouver, BC Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
authors.affiliation: Department of Cellular and Physiological Sciences; University of British Columbia; Vancouver, BC Canada.
authors.forename: Yin Nam
authors.initials: YN
authors.lastname: Kwok
authors.affiliation: School of Life Sciences; University of Warwick; Coventry, West Midlands, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dale
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004176:Dipyridamole / Q000494:pharmacology; D005089:Exocytosis; D045604:Extracellular Fluid / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D033703:Nucleoside Transport Proteins; D013868:Thioinosine; D004176:Dipyridamole; D011189:Potassium Chloride; D006157:Guanosine Monophosphate; C001789:4-nitrobenzylthioinosine; D005947:Glucose; D000241:Adenosine; D002118:Calcium