PMID- 15231713
OWN - NLM
STAT- MEDLINE
DCOM- 20040928
LR  - 20181217
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 145
IP  - 9
DP  - 2004 Sep
TI  - Impaired glucose-stimulated insulin secretion, enhanced intraperitoneal insulin 
      tolerance, and increased beta-cell mass in mice lacking the p110gamma isoform of 
      phosphoinositide 3-kinase.
PG  - 4078-83
AB  - Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled 
      receptor regulation of pancreatic beta-cell growth and glucose-stimulated insulin 
      secretion. The G protein-activated p110gamma isoform of PI3 kinase was detected 
      in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, 
      knockout of p110gamma 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 p110gamma -/- 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 p110gamma 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 p110gamma -/- 
      mice had greater pancreatic insulin content, and an increased beta-cell mass due 
      to beta-cell hypertrophy. These surprising results suggest that the G 
      protein-coupled p110gamma isoform of PI3 kinase is not central to the development 
      or maintenance of sufficient beta-cell mass but positively regulates 
      glucose-stimulated insulin secretion.
FAU - MacDonald, P E
AU  - MacDonald PE
AD  - University of Toronto, Department of Physiology, Toronto, Canada. 
      patrick.macdonald@mphy.lu.se.
FAU - Joseph, J W
AU  - Joseph JW
FAU - Yau, D
AU  - Yau D
FAU - Diao, J
AU  - Diao J
FAU - Asghar, Z
AU  - Asghar Z
FAU - Dai, F
AU  - Dai F
FAU - Oudit, G Y
AU  - Oudit GY
FAU - Patel, M M
AU  - Patel MM
FAU - Backx, P H
AU  - Backx PH
FAU - Wheeler, M B
AU  - Wheeler MB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040701
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Insulin)
RN  - 0 (Isoenzymes)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.137 (PIK3CG protein, human)
RN  - EC 2.7.1.153 (Pik3cg protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Class Ib Phosphatidylinositol 3-Kinase
MH  - Exenatide
MH  - Glucose/pharmacology
MH  - Homeostasis/physiology
MH  - Injections, Intraperitoneal
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/*enzymology/metabolism
MH  - Isoenzymes/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Peptides/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*genetics/metabolism
MH  - Venoms/pharmacology
EDAT- 2004/07/03 05:00
MHDA- 2004/09/29 05:00
CRDT- 2004/07/03 05:00
PHST- 2004/07/03 05:00 [pubmed]
PHST- 2004/09/29 05:00 [medline]
PHST- 2004/07/03 05:00 [entrez]
AID - en.2004-0028 [pii]
AID - 10.1210/en.2004-0028 [doi]
PST - ppublish
SO  - Endocrinology. 2004 Sep;145(9):4078-83. doi: 10.1210/en.2004-0028. Epub 2004 Jul 
      1.