Absence of adenosine A(1) receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin
2009 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 85, no 11-12, 470-476 p.Article in journal (Refereed) Published
Aims: Extracellular ATP modulates pulsatile release of insulin, glucagon and somatostatin by activating P2Y(1) receptors. The present study examines if adenosine via A(1) receptors (A(1)R) interferes with pulsatile islet hormone release. Main methods: Pancreas was perfused in mice expressing or lacking the A(1) receptor and the hormones measured with radioimmunoassay. Cytoplasmic Ca2+ was recorded in isolated beta-cells using the fura-2 indicator. Key findings: Addition of 10 mu M adenosine removed the Ca2+ transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100 nM of the A(1)R antagonist DPCPX. In situ perfusion of the pancreas indicated two phases of islet hormone release when glucose was raised from 3.3 to 16.7 mM. The first phase was characterized by a brief dip followed by a peak which was more pronounced for insulin and somatostatin than for glucagon. The second phase was markedly affected by knock out of A(1)R. The wild-type AIR (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4 min. In the A(1)R (-/-) mice time-average release of insulin during the second phase was almost three times higher than in the controls and 30% of the hormone was released as distinct pulses with half-widths of 3 min. The absence of the AIR receptor resulted in 50% prolongation of the pulse cycles of glucagon and somatostatin and loss of their antisynchronous relationship. Significance: The A(1)R receptor is important both for the amplitude (insulin) and duration (glucagon and somatostatin) of islet hormone pulses. (C) 2009 Elsevier Inc. All rights reserved.
Place, publisher, year, edition, pages
2009. Vol. 85, no 11-12, 470-476 p.
Calcium signalling, Pancreas perfusion, Pancreatic beta-cells, DPCPX, Synchronization
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-128256DOI: 10.1016/j.lfs.2009.08.001ISI: 000270013000009OAI: oai:DiVA.org:uu-128256DiVA: diva2:330993