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Defective secretion of islet hormones in chromogranin-B deficient mice.

Obermüller, Stefanie LU ; Calegari, Federico ; King, Angus ; Lindqvist, Anders LU ; Lundquist, Ingmar LU ; Salehi, S Albert LU orcid ; Francolini, Maura ; Rosa, Patrizia ; Rorsman, Patrik LU and Huttner, Wieland B , et al. (2010) In PLoS ONE 5(1).
Abstract
Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced... (More)
Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
5
issue
1
article number
e8936
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000274138000014
  • pmid:20126668
  • scopus:77749251923
  • pmid:20126668
ISSN
1932-6203
DOI
10.1371/journal.pone.0008936
language
English
LU publication?
yes
id
a29449ec-1c94-46c6-9d9b-bb677e1d6cea (old id 1553005)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20126668?dopt=Abstract
date added to LUP
2016-04-04 09:15:00
date last changed
2022-03-15 18:26:02
@article{a29449ec-1c94-46c6-9d9b-bb677e1d6cea,
  abstract     = {{Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined.}},
  author       = {{Obermüller, Stefanie and Calegari, Federico and King, Angus and Lindqvist, Anders and Lundquist, Ingmar and Salehi, S Albert and Francolini, Maura and Rosa, Patrizia and Rorsman, Patrik and Huttner, Wieland B and Barg, Sebastian}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Defective secretion of islet hormones in chromogranin-B deficient mice.}},
  url          = {{https://lup.lub.lu.se/search/files/5272745/1578783.pdf}},
  doi          = {{10.1371/journal.pone.0008936}},
  volume       = {{5}},
  year         = {{2010}},
}