Inhibition of purinoceptors amplifies glucose-stimulated insulin release with removal of its pulsatility
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/233885
- author
- Salehi, S Albert LU ; Quader, SS ; Grapengiesser, E and Hellman, B
- organization
- publishing date
- 2005
- 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
- 2016-04-01 16:10:21
- date last changed
- 2019-05-28 02:19:12
@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 < 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.}}, 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}}, url = {{http://diabetes.diabetesjournals.org/cgi/content/abstract/54/7/2126}}, volume = {{54}}, year = {{2005}}, }