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Diabetes 54:1064-1073, 2005
© 2005 by the American Diabetes Association, Inc.

Neuronatin, a Downstream Target of BETA2/NeuroD1 in the Pancreas, Is Involved in Glucose-Mediated Insulin Secretion

Khoi Chu1, and Ming-Jer Tsai1,2

1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas
2 Developmental Biology Program, Baylor College of Medicine, Houston, Texas

BETA2 (NeuroD1) is a member of the basic helix-loop-helix transcription factor family. BETA2 plays an important role in the development of the pancreas and the nervous system. Using microarray technology, we identified neuronatin (Nnat) as differentially expressed between wild-type (WT) and knockout (KO) pancreatic RNA from embryonic day 14 (e14.5). NNAT is a member of the proteolipid family of amphipathic polypeptides and is believed to be involved in ion channel transport or channel modulation. Northern blot and in situ hybridization analysis of WT and KO samples confirmed the downregulation of Nnat in pancreas of mutant BETA2 embryos. Chromatin immunoprecipitation and gel shift assays were performed and demonstrated the presence of BETA2 on the Nnat promoter, thus confirming the direct transcriptional regulation of Nnat by BETA2. To assess NNAT potential function, we performed knockdown studies by siRNA in NIT cells and observed a reduction in the ability of the NIT cells to respond to glucose. These results suggest for the first time an important role for NNAT in insulin secretion and for proper ß-cell function.


Address correspondence and reprint requests to Ming-Jer Tsai, PhD, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: mtsai{at}bcm.tmc.edu


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Mol Biol EvolHome page
H. K. Evans, J. R. Weidman, D. O. Cowley, and R. L. Jirtle
Comparative Phylogenetic Analysis of Blcap/Nnat Reveals Eutherian-Specific Imprinted Gene
Mol. Biol. Evol., August 1, 2005; 22(8): 1740 - 1748.
[Abstract] [Full Text] [PDF]




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