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BIG 3 inhibits insulin granule biogenesis and insulin secretion
Author(s) -
Li Hongyu,
Wei Shunhui,
Cheng Kenneth,
Gounko Natalia V,
Ericksen Russell E,
Xu Aimin,
Hong Wanjin,
Han Weiping
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1002/embr.201338181
Subject(s) - china , agency (philosophy) , library science , political science , sociology , social science , law , computer science
Abstract While molecular regulation of insulin granule exocytosis is relatively well understood, insulin granule biogenesis and maturation and its influence on glucose homeostasis are relatively unclear. Here, we identify a novel protein highly expressed in insulin‐secreting cells and name it BIG 3 due to its similarity to BIG / GBF of the Arf‐ GTP exchange factor (GEF ) family. BIG 3 is predominantly localized to insulin‐ and clathrin‐positive trans‐Golgi network ( TGN ) compartments. BIG 3‐deficient insulin‐secreting cells display increased insulin content and granule number and elevated insulin secretion upon stimulation. Moreover, BIG 3 deficiency results in faster processing of proinsulin to insulin and chromogranin A to β‐granin in β‐cells. BIG 3 ‐knockout mice exhibit postprandial hyperinsulinemia, hyperglycemia, impaired glucose tolerance, and insulin resistance. Collectively, these results demonstrate that BIG 3 negatively modulates insulin granule biogenesis and insulin secretion and participates in the regulation of systemic glucose homeostasis.