PMID- 22125081
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20211203
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 821
DP  - 2012
TI  - Tissue-specific ablation of Tsc1 in pancreatic beta-cells.
PG  - 407-19
LID - 10.1007/978-1-61779-430-8_26 [doi]
AB  - Tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that associates with 
      TSC2 to inactivate Rheb, thereby inhibiting signaling by the mammalian target of 
      rapamycin (mTOR) complex 1 (mTORC1). mTORC1 stimulates cell growth by promoting 
      anabolic cellular processes, such as translation, in response to growth factors 
      and nutrient signals. In order to test roles for TSC1 and mTORC1 in beta-cell 
      function, we utilized Rip2/Cre to generate mice lacking Tsc1 in pancreatic beta 
      cells (Rip-Tsc1cKO mice). While obesity developed due to hypothalamic Tsc1 
      excision in older Rip-Tsc1cKO animals, young animals displayed a prominent 
      gain-of-function beta-cell phenotype prior to the onset of obesity. The young 
      Rip-Tsc1cKO animals displayed improved glycemic control due to mTOR-mediated 
      enhancement of beta-cell size and insulin production, but not beta-cell number 
      consistent with an important anabolic role for mTOR in beta-cell function. Thus, 
      mTOR promulgates a dominant signal to promote beta-cell/islet size and insulin 
      production, and this pathway is crucial for beta-cell function and glycemic control. 
      Here, we describe the methods of analyzing tissue-specific ablation of Tsc1 in 
      pancreatic beta cells.
FAU - Mori, Hiroyuki
AU  - Mori H
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA. morimori@umich.edu
FAU - Guan, Kun-Liang
AU  - Guan KL
LA  - eng
GR  - R01 CA108941/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Insulin)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (TSC1 protein, human)
RN  - 0 (Tsc1 protein, mouse)
RN  - 0 (Tsc1 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Gene Knockout Techniques/*methods
MH  - Humans
MH  - Insulin/genetics/metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Multiprotein Complexes
MH  - Promoter Regions, Genetic
MH  - Proteins/*genetics/metabolism
MH  - Rats
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis/genetics
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tumor Suppressor Proteins/*genetics
EDAT- 2011/11/30 06:00
MHDA- 2012/03/17 06:00
CRDT- 2011/11/30 06:00
PHST- 2011/11/30 06:00 [entrez]
PHST- 2011/11/30 06:00 [pubmed]
PHST- 2012/03/17 06:00 [medline]
AID - 10.1007/978-1-61779-430-8_26 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2012;821:407-19. doi: 10.1007/978-1-61779-430-8_26.