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Absence of adenosine A(1) receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin.

Salehi, S Albert LU ; Parandeh, Fariborz; Fredholm, Bertil B; Grapengiesser, Eva and Hellman, Bo (2009) In Life Sciences 85. p.470-476
Abstract
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 Ca(2+) was recorded in isolated beta-cells using the fura-2 indicator. KEY FINDINGS: Addition of 10microM adenosine removed the Ca(2+) transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100nM of the A(1)R antagonist DPCPX. In situ perfusion of the pancreas indicated two phases of islet hormone release when... (More)
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 Ca(2+) was recorded in isolated beta-cells using the fura-2 indicator. KEY FINDINGS: Addition of 10microM adenosine removed the Ca(2+) transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100nM 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 16.7mM. 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 A(1)R (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4min. 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 3min. The absence of the A(1)R 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Life Sciences
volume
85
pages
470 - 476
publisher
Elsevier
external identifiers
  • wos:000270013000009
  • pmid:19682463
  • scopus:69349102048
ISSN
1879-0631
DOI
10.1016/j.lfs.2009.08.001
language
English
LU publication?
yes
id
3c0af292-697e-45df-9cbe-50c8330fdb51 (old id 1469704)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19682463?dopt=Abstract
date added to LUP
2009-09-03 15:04:04
date last changed
2017-10-22 04:52:53
@article{3c0af292-697e-45df-9cbe-50c8330fdb51,
  abstract     = {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 Ca(2+) was recorded in isolated beta-cells using the fura-2 indicator. KEY FINDINGS: Addition of 10microM adenosine removed the Ca(2+) transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100nM 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 16.7mM. 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 A(1)R (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4min. 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 3min. The absence of the A(1)R 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.},
  author       = {Salehi, S Albert and Parandeh, Fariborz and Fredholm, Bertil B and Grapengiesser, Eva and Hellman, Bo},
  issn         = {1879-0631},
  language     = {eng},
  pages        = {470--476},
  publisher    = {Elsevier},
  series       = {Life Sciences},
  title        = {Absence of adenosine A(1) receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin.},
  url          = {http://dx.doi.org/10.1016/j.lfs.2009.08.001},
  volume       = {85},
  year         = {2009},
}