ArticleMolecular metabolism2015
Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes.Diabetes care · 2024Pooled it
- Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage.BMC genomics · 2023Article
- Misrouting of glucagon and stathmin-2 towards lysosomal system of α-cells in glucagon hypersecretion of diabetes.Islets · 2022Article
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics).Molecular & cellular proteomics : MCP · 2018Article
- Plasticity in the Glucagon Interactome Reveals Novel Proteins That Regulate Glucagon Secretion in α-TC1-6 Cells.Frontiers in endocrinology · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAlthough 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.
methodsWe 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.
resultsBIG3 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.
conclusionsTogether 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.
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