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Inhibition of purinoceptors amplifies glucose-stimulated insulin release with removal of its pulsatility

Salehi, S Albert LU ; Quader, SS; Grapengiesser, E and Hellman, B (2005) In Diabetes 54(7). p.2126-2131
Abstract
External ATP has been proposed to be an autocrine regulator of glucose-stimulated insulin secretion and responsible for the synchronization of the Ca2+ rhythmicity in the P-cells required for a pulsatile release of insulin from the pancreas. The importance of external ATP for glucose-stimulated insulin release was evaluated in rats with the aid of 2-deoxy-N-methyladenosine3,5-bisphosphate (MRS 2179), an inhibitor of the purinoceptors known to affect the Ca2+ signaling in R-cells. The concentration of cytoplasmic Ca2+ was measured in single P-cells and small aggregates with ratiometric fura-2 technique and the release of insulin recorded from isolated islets and the perfused pancreas. Addition of 1 mu mol/l ATP induced premature cytoplasmic... (More)
External ATP has been proposed to be an autocrine regulator of glucose-stimulated insulin secretion and responsible for the synchronization of the Ca2+ rhythmicity in the P-cells required for a pulsatile release of insulin from the pancreas. The importance of external ATP for glucose-stimulated insulin release was evaluated in rats with the aid of 2-deoxy-N-methyladenosine3,5-bisphosphate (MRS 2179), an inhibitor of the purinoceptors known to affect the Ca2+ signaling in R-cells. The concentration of cytoplasmic Ca2+ was measured in single P-cells and small aggregates with ratiometric fura-2 technique and the release of insulin recorded from isolated islets and the perfused pancreas. Addition of 1 mu mol/l ATP induced premature cytoplasmic Ca2+ concentration ([Ca2+](i)) oscillations similar to those found in P-cells exposed to 20 mmol/l glucose. In most experiments, the presence of 10 mu mol/l MRS 2179 did not remove the glucose-induced [Ca2+] rhythmicity in single R-cells or the synchronization seen in coupled cells. Nevertheless, the same concentration of MRS 2179 promptly interrupted the pulsatility (frequency 0.22 +/- 0.01/min) of insulin secretion, raising the total amounts released from the pancreas. Prolonged exposure of islets to 1 and 10 mu molA MRS 2179 enhanced insulin secretion at 20 mmol/l glucose 33% (P < 0.05) and 63% (P < 0.01), respectively, without affecting the release at 3 mmol/l glucose. The results support the idea that neural ATP signals entrain the islets into a common rhythm resulting in pulsatile release of insulin and that glucose stimulation of the secretory activity is counteracted by accumulation of inhibitory ATP around the beta-cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
54
issue
7
pages
2126 - 2131
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000230164000027
  • pmid:15983214
ISSN
1939-327X
language
English
LU publication?
yes
id
e8f210cf-add9-48ee-9a78-22778cfd711e (old id 233885)
alternative location
http://diabetes.diabetesjournals.org/cgi/content/abstract/54/7/2126
date added to LUP
2007-08-15 14:57:52
date last changed
2016-04-16 03:56:27
@article{e8f210cf-add9-48ee-9a78-22778cfd711e,
  abstract     = {External ATP has been proposed to be an autocrine regulator of glucose-stimulated insulin secretion and responsible for the synchronization of the Ca2+ rhythmicity in the P-cells required for a pulsatile release of insulin from the pancreas. The importance of external ATP for glucose-stimulated insulin release was evaluated in rats with the aid of 2-deoxy-N-methyladenosine3,5-bisphosphate (MRS 2179), an inhibitor of the purinoceptors known to affect the Ca2+ signaling in R-cells. The concentration of cytoplasmic Ca2+ was measured in single P-cells and small aggregates with ratiometric fura-2 technique and the release of insulin recorded from isolated islets and the perfused pancreas. Addition of 1 mu mol/l ATP induced premature cytoplasmic Ca2+ concentration ([Ca2+](i)) oscillations similar to those found in P-cells exposed to 20 mmol/l glucose. In most experiments, the presence of 10 mu mol/l MRS 2179 did not remove the glucose-induced [Ca2+] rhythmicity in single R-cells or the synchronization seen in coupled cells. Nevertheless, the same concentration of MRS 2179 promptly interrupted the pulsatility (frequency 0.22 +/- 0.01/min) of insulin secretion, raising the total amounts released from the pancreas. Prolonged exposure of islets to 1 and 10 mu molA MRS 2179 enhanced insulin secretion at 20 mmol/l glucose 33% (P &lt; 0.05) and 63% (P &lt; 0.01), respectively, without affecting the release at 3 mmol/l glucose. The results support the idea that neural ATP signals entrain the islets into a common rhythm resulting in pulsatile release of insulin and that glucose stimulation of the secretory activity is counteracted by accumulation of inhibitory ATP around the beta-cells.},
  author       = {Salehi, S Albert and Quader, SS and Grapengiesser, E and Hellman, B},
  issn         = {1939-327X},
  language     = {eng},
  number       = {7},
  pages        = {2126--2131},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Inhibition of purinoceptors amplifies glucose-stimulated insulin release with removal of its pulsatility},
  volume       = {54},
  year         = {2005},
}