PMID- 20555035
OWN - NLM
STAT- MEDLINE
DCOM- 20100908
LR  - 20211020
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 151
IP  - 8
DP  - 2010 Aug
TI  - Multiple endocrine neoplasia type 1 deletion in pancreatic alpha-cells leads to 
      development of insulinomas in mice.
PG  - 4024-30
LID - 10.1210/en.2009-1251 [doi]
AB  - The pancreatic alpha- and beta-cells are critical components in regulating blood 
      glucose homeostasis via secretion of glucagon and insulin, respectively. Both 
      cell types are typically localized in the islets of Langerhans. However, little 
      is known about the roles of paracrine interactions that contribute to their 
      physiological functions. The lack of suitable cell lines to study alpha- and 
      beta-cells interactions have led us to develop an alpha-cell-specific 
      Cre-expressing transgenic line utilizing a glucagon promoter sequence, the 
      Glu-Cre transgenic mouse. Here, we demonstrate that the Glu-Cre could 
      specifically and efficiently excise floxed target genes in adult islet 
      alpha-cells. We further showed that deletion of the tumor suppressor gene, 
      multiple endocrine neoplasia type 1 (Men1), in alpha-cells led to tumorigenesis. 
      However, to our surprise, the lack of Men1 in alpha-cells did not result in 
      glucagonomas but rather beta-cell insulinomas. Because deletion of the Men1 
      alleles was only present in alpha-cells, our data suggested that cross 
      communication between alpha- and beta-cells contributes to tumorigenesis in the 
      absence of Men1. Together, we believed that the new model systems described here 
      will allow future studies to decipher cellular interactions between islet alpha- 
      and beta-cells in a physiological context.
FAU - Shen, H-C Jennifer
AU  - Shen HC
AD  - Tissue Array Research Program, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-8322, 
      USA.
FAU - Ylaya, Kris
AU  - Ylaya K
FAU - Pechhold, Klaus
AU  - Pechhold K
FAU - Wilson, Arianne
AU  - Wilson A
FAU - Adem, Asha
AU  - Adem A
FAU - Hewitt, Stephen M
AU  - Hewitt SM
FAU - Libutti, Steven K
AU  - Libutti SK
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20100616
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Gene Deletion
MH  - Gene Knockdown Techniques
MH  - Glucagon/genetics/metabolism
MH  - Glucagon-Secreting Cells/*metabolism
MH  - Insulinoma/*genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Organ Specificity/genetics
MH  - Pancreatic Neoplasms/*genetics/metabolism
MH  - Proto-Oncogene Proteins/*genetics/metabolism
PMC - PMC2940531
EDAT- 2010/06/18 06:00
MHDA- 2010/09/09 06:00
PMCR- 2011/08/01
CRDT- 2010/06/18 06:00
PHST- 2010/06/18 06:00 [entrez]
PHST- 2010/06/18 06:00 [pubmed]
PHST- 2010/09/09 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - en.2009-1251 [pii]
AID - 5499 [pii]
AID - 10.1210/en.2009-1251 [doi]
PST - ppublish
SO  - Endocrinology. 2010 Aug;151(8):4024-30. doi: 10.1210/en.2009-1251. Epub 2010 Jun 
      16.