TY - JOUR T1 - NFIA regulates granule recruitment and exocytosis in the adult pancreas JF - bioRxiv DO - 10.1101/2019.12.24.885020 SP - 2019.12.24.885020 AU - Marissa A. Scavuzzo AU - Jolanta Chmielowiec AU - Jessica Teaw AU - Diane Yang AU - Matthew C. Hill AU - Andrea R. Waksmunski AU - Lita Duraine AU - Joan Camunas-Soler AU - Xiaoqing Dai AU - Jordon C. King AU - Stephen R Quake AU - Patrick E. MacDonald AU - Andre Catic AU - Malgorzata Borowiak Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/12/26/2019.12.24.885020.abstract N2 - After food ingestion, pancreatic cells secrete zymogen and hormone-containing granules to precisely control digestion and blood glucose levels. Identifying regulators of this process is paramount to combatting multiple pancreatic diseases. Here we show that pancreatic deletion of the transcription factor nuclear factor IA (NFIA) leads to hyperglycemia, hypoinsulinemia, and hypolipidemia. Surprisingly, insulin and digestive enzymes are produced in the absence of NFIA, however, they are not secreted properly and instead accumulate inside pancreatic cells. In NFIA-deficient mice we saw a reduction of insulin granules in the ready releasable pool and the first-phase insulin response was impaired. We found that NFIA binds to and activates Rab39b, a Rab GTPase critical for exocytosis. Re-expression of Rab39b in NFIA knockout islets restored glucose-stimulated insulin secretion. In sum, the NFIA-Rab39b axis regulates pancreatic physiology through granule recruitment and docking, linking NFIA to a new process with potential effects in diabetes, pancreatitis, and lipid disorders. ER -