Impaired glucose-stimulated insulin secretion, enhanced IP insulin tolerance and increased {beta}-cell mass in mice lacking the p110{gamma} isoform of PI3-kinase.
(2004) In Endocrinology 145(9). p.4078-4083- Abstract
- Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic ß-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110{gamma} isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110{gamma} reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110{gamma} –/– mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking... (More)
- Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic ß-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110{gamma} isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110{gamma} reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110{gamma} –/– mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking p110{gamma} were not diabetic and were only slightly glucose intolerant (ip glucose injection) compared with wild types, in part due to enhanced responsiveness to insulin as determined by an ip insulin tolerance test. Despite severely reduced insulin secretion in these animals, the p110{gamma} –/– mice had greater pancreatic insulin content, and an increased ß-cell mass due to ß-cell hypertrophy. These surprising results suggest that the G protein-coupled p110{gamma} isoform of PI3 kinase is not central to the development or maintenance of sufficient ß-cell mass but positively regulates glucose-stimulated insulin secretion. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/126039
- author
- MacDonald, Patrick LU ; Joseph, J. W. ; Yau, D. ; Diao, J. ; Asghar, Z. ; Dai, F. ; Oudit, G. Y. ; Patel, M. M. ; Backx, P. H. and Wheeler, M. B.
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Endocrinology
- volume
- 145
- issue
- 9
- pages
- 4078 - 4083
- publisher
- Oxford University Press
- external identifiers
-
- wos:000223401600014
- pmid:15231713
- scopus:4344571667
- ISSN
- 0013-7227
- DOI
- 10.1210/en.2004-0028
- language
- English
- LU publication?
- yes
- id
- c3a6b048-a832-4633-9d77-df5bdc1836a9 (old id 126039)
- date added to LUP
- 2016-04-01 12:11:59
- date last changed
- 2022-01-27 00:16:20
@article{c3a6b048-a832-4633-9d77-df5bdc1836a9,
abstract = {{Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic ß-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110{gamma} isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110{gamma} reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110{gamma} –/– mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking p110{gamma} were not diabetic and were only slightly glucose intolerant (ip glucose injection) compared with wild types, in part due to enhanced responsiveness to insulin as determined by an ip insulin tolerance test. Despite severely reduced insulin secretion in these animals, the p110{gamma} –/– mice had greater pancreatic insulin content, and an increased ß-cell mass due to ß-cell hypertrophy. These surprising results suggest that the G protein-coupled p110{gamma} isoform of PI3 kinase is not central to the development or maintenance of sufficient ß-cell mass but positively regulates glucose-stimulated insulin secretion.}},
author = {{MacDonald, Patrick and Joseph, J. W. and Yau, D. and Diao, J. and Asghar, Z. and Dai, F. and Oudit, G. Y. and Patel, M. M. and Backx, P. H. and Wheeler, M. B.}},
issn = {{0013-7227}},
language = {{eng}},
number = {{9}},
pages = {{4078--4083}},
publisher = {{Oxford University Press}},
series = {{Endocrinology}},
title = {{Impaired glucose-stimulated insulin secretion, enhanced IP insulin tolerance and increased {beta}-cell mass in mice lacking the p110{gamma} isoform of PI3-kinase.}},
url = {{http://dx.doi.org/10.1210/en.2004-0028}},
doi = {{10.1210/en.2004-0028}},
volume = {{145}},
year = {{2004}},
}