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Impaired glucose-stimulated insulin secretion, enhanced IP insulin tolerance and increased {beta}-cell mass in mice lacking the p110{gamma} isoform of PI3-kinase.

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. (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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
145
issue
9
pages
4078 - 4083
publisher
Endocrine Society
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
2007-07-17 11:33:38
date last changed
2017-10-22 03:47:51
@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    = {Endocrine Society},
  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},
  volume       = {145},
  year         = {2004},
}