daibetes

flydayzhu

http://www.ncbi.nlm.nih.gov/pubm ... 20and%20Cell%20Size
  e9 x6 N4 ]" Q% LDiabetes. 2011 Jan 24. [Epub ahead of print]; D) ?7 n: t, B- E8 S
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Rictor/mTORC2 Is Essential for Maintaining a Balance Between {beta}-Cell Proliferation and Cell Size.; d9 w2 B" _0 z$ ]
Gu Y, Lindner J, Kumar A, Yuan W, Magnuson MA.+ n0 r! @! B( E1 h" G& T# i& L5 T0 n
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Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee." {$ B3 m& i' A  K

# W- [. B; d+ V! h/ e9 V7 L" ^5 FAbstract/ q) y2 i$ Y* ^' r
OBJECTIVE We examined the role of Rictor/mammalian target of rapamycin complex 2 (mTORC2), a key component of the phosphotidylinositol-3-kinase (PI3K)/mTORC2/AKT signaling pathway, in regulating both β-cell mass and function. RESEARCH DESIGN AND METHODS Mice with β-cell-specific deletions of Rictor or Pten were studied to determine the effects of deleting either or both genes on β-cell mass and glucose homeostasis. RESULTS Rictor null mice exhibited mild hyperglycemia and glucose intolerance caused by a reduction in β-cell mass, β-cell proliferation, pancreatic insulin content, and glucose-stimulated insulin secretion. Islets from these mice exhibited decreased AKT-S473 phosphorylation and increased abundance of FoxO1 and p27 proteins. Conversely, Pten null (βPtenKO) mice exhibited an increase in β-cell mass caused by increased cellular proliferation and size. Although β-cell mass was normal in mice lacking both Rictor and Pten (βDKO), their β-cells were larger than those in the βPtenKO mice. Even though the β-cell proliferation rate in the βDKO mice was lower than in the βPtenKO mice, there was a 12-fold increase the phosphorylation of AKT-T308. CONCLUSIONS PI3K/AKT signaling through mTORC2/pAKT-S473 plays a key role in maintaining normal β-cell mass. The phosphorylation of AKT-S473, by negatively regulating that of AKT-T308, is essential for maintaining a balance between β-cell proliferation and cell size in response to proliferative stimuli.! P! t% G+ q7 }6 \
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PMID: 21266327 [PubMed - as supplied by publisher]

inankai

Diabetes. 2011 Jan 24. [Epub ahead of print]0 n; L: Q6 h$ h* M
Rictor/mTORC2 Is Essential for Maintaining a Balance Between {beta}-Cell Proliferation and Cell Size.) X2 k5 S, V  X; W( M; \* w

9 Z& |) {! ~$ j! T" |4 uGu Y, Lindner J, Kumar A, Yuan W, Magnuson MA.6 p" q: Y1 {' p; ~  y: r, X! o
' l( F0 K4 j2 o; n# c* U
Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee.  [; j7 o& o8 _; z- @7 n' B
Abstract: u+ h  q7 Z8 k7 m9 |+ n
2 k! H2 j" q& X
OBJECTIVE We examined the role of Rictor/mammalian target of rapamycin complex 2 (mTORC2), a key component of the phosphotidylinositol-3-kinase (PI3K)/mTORC2/AKT signaling pathway, in regulating both β-cell mass and function. RESEARCH DESIGN AND METHODS Mice with β-cell-specific deletions of Rictor or Pten were studied to determine the effects of deleting either or both genes on β-cell mass and glucose homeostasis. RESULTS Rictor null mice exhibited mild hyperglycemia and glucose intolerance caused by a reduction in β-cell mass, β-cell proliferation, pancreatic insulin content, and glucose-stimulated insulin secretion. Islets from these mice exhibited decreased AKT-S473 phosphorylation and increased abundance of FoxO1 and p27 proteins. Conversely, Pten null (βPtenKO) mice exhibited an increase in β-cell mass caused by increased cellular proliferation and size. Although β-cell mass was normal in mice lacking both Rictor and Pten (βDKO), their β-cells were larger than those in the βPtenKO mice. Even though the β-cell proliferation rate in the βDKO mice was lower than in the βPtenKO mice, there was a 12-fold increase the phosphorylation of AKT-T308. CONCLUSIONS PI3K/AKT signaling through mTORC2/pAKT-S473 plays a key role in maintaining normal β-cell mass. The phosphorylation of AKT-S473, by negatively regulating that of AKT-T308, is essential for maintaining a balance between β-cell proliferation and cell size in response to proliferative stimuli.

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