Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta -cell exocytosis and release of insulin.
Härndahl, Linda LU ; Jing, Xingjun LU ; Ivarsson, Rosita LU ; Degerman, Eva LU
; Ahrén, Bo
LU
; Manganiello, Vincent C.
; Renström, Erik
LU
and Stenson Holst, Lena
(2002)
In Journal of Biological Chemistry
277(40).
p.37446-37455
- Abstract
- Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic b-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on b-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly... (More)
- Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic b-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on b-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13), and insulin secretion in response to stimulation with high glucose (11.1 mM) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nM) to augment glucose-stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single b-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 mM) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109842
- author
- Härndahl, Linda
LU
; Jing, Xingjun
LU
; Ivarsson, Rosita
LU
; Degerman, Eva
LU
; Ahrén, Bo
LU
; Manganiello, Vincent C.
; Renström, Erik
LU
and Stenson Holst, Lena
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 277
- issue
- 40
- pages
- 37446 - 37455
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000178447100069
- scopus:0037020258
- pmid:12169692
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M205401200
- language
- English
- LU publication?
- yes
- id
- e69a0cd3-75ee-46bb-b656-b2b9a9a0adde (old id 109842)
- alternative location
- http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12169692&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- date added to LUP
- 2016-04-01 12:02:40
- date last changed
- 2024-01-23 04:07:42
@article{e69a0cd3-75ee-46bb-b656-b2b9a9a0adde,
abstract = {{Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic b-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on b-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13), and insulin secretion in response to stimulation with high glucose (11.1 mM) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nM) to augment glucose-stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single b-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 mM) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes.}},
author = {{Härndahl, Linda and Jing, Xingjun and Ivarsson, Rosita and Degerman, Eva and Ahrén, Bo and Manganiello, Vincent C. and Renström, Erik and Stenson Holst, Lena}},
issn = {{1083-351X}},
language = {{eng}},
number = {{40}},
pages = {{37446--37455}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta -cell exocytosis and release of insulin.}},
url = {{http://dx.doi.org/10.1074/jbc.M205401200}},
doi = {{10.1074/jbc.M205401200}},
volume = {{277}},
year = {{2002}},
}