TY - JOUR
T1 - Dysregulation of Dicer1 in beta cells impairs islet architecture and glucose metabolism
AU - Mandelbaum, Amitai D.
AU - Melkman-Zehavi, Tal
AU - Oren, Roni
AU - Kredo-Russo, Sharon
AU - Nir, Tomer
AU - Dor, Yuval
AU - Hornstein, Eran
N1 - Juvenile Diabetes Research Foundation [99-2007-71, 47-2012-742]; EFSD/D-Cure young Investigator award, EFSD-Lilly; Israel Science Foundation; Wolfson family charitable trustThe authors thank Brain Harfe, Mike McManus, and Cliff Tabin for the Dicer1 conditional allele Mark Magnuson for RIP-Cre, Rolf Kemler for conditional Cdh1 allele Frank Costantini for Rosa-EYFP reporter. This work was supported by Grants to E. Hornstein from Juvenile Diabetes Research Foundation (no. 99-2007-71 and no. 47-2012-742), the EFSD/D-Cure young Investigator award, EFSD-Lilly, the Israel Science Foundation, and the Wolfson family charitable trust. E. Hornstein is the incumbent of the Helen and Milton A. Kimmelman Career Development Chair and the Dr. Sydney Brenner Chair.
PY - 2012
Y1 - 2012
N2 - microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.
AB - microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.
UR - http://www.scopus.com/inward/record.url?scp=84867028085&partnerID=8YFLogxK
U2 - https://doi.org/10.1155/2012/470302
DO - https://doi.org/10.1155/2012/470302
M3 - مقالة
C2 - 22991506
SN - 1687-5214
VL - 2012
JO - Experimental Diabetes Research
JF - Experimental Diabetes Research
M1 - 470302
ER -