Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice

Abstract Objective Although both insulin and glucagon are intimately involved in the regulation of glucose homeostasis, the intrinsic control of glucagon secretion, including the biogenesis and exocytosis of glucagon-containing granules, is far less understood compared with that of insulin. As Brefe...

Full description

Saved in:
Bibliographic Details
Published in:Molecular metabolism (Germany) 2015-03, Vol.4 (3), p.246-252
Main Authors: Li, Hongyu, Liu, Tao, Lim, Joy, Gounko, Natalia V, Hong, Wanjin, Han, Weiping
Format: Article
Language:English
Subjects:
Alpha-cell
BIG3
Brief Communication
Diabetes
Endocrinology & Metabolism
Exocytosis
Glucagon
Glucose homeostasis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Objective Although both insulin and glucagon are intimately involved in the regulation of glucose homeostasis, the intrinsic control of glucagon secretion, including the biogenesis and exocytosis of glucagon-containing granules, is far less understood compared with that of insulin. As Brefeldin A-inhibited guanine nucleotide exchange protein 3 (BIG3) is a negative regulator of insulin-granule biogenesis and insulin secretion, we investigated whether BIG3 plays any role in alpha-cells and glucagon secretion. Methods We examined the expression of BIG3 in islet cells by immuno-fluorescence and confocal microscopy, and measured glucagon production and secretion in BIG3-depleted and wild-type mice, islets and cells. Results BIG3 is highly expressed in pancreatic alpha-cells in addition to beta-cells, but is absent in delta-cells. Depletion of BIG3 in alpha-cells leads to elevated glucagon production and secretion. Consistently, BIG3-knockout (BKO) mice display increased glucagon release under hypoglycemic conditions. Conclusions Together with our previous studies, the current data reveal a conserved role for BIG3 in regulating alpha- and beta-cell functions. We propose that BIG3 negatively regulates hormone production at the secretory granule biogenesis stage and that such regulatory mechanism may be used in secretory pathways of other endocrine cells.
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2015.01.001