Defective secretion of islet hormones in chromogranin-B deficient mice.
Författare
Summary, in English
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.
Avdelning/ar
- Islet cell physiology
- Drug Target Discovery
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2010
Språk
Engelska
Publikation/Tidskrift/Serie
PLoS ONE
Volym
5
Issue
1
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Public Library of Science (PLoS)
Ämne
- Pharmacology and Toxicology
- Endocrinology and Diabetes
Status
Published
Forskningsgrupp
- Islet cell physiology
- Drug Target Discovery
ISBN/ISSN/Övrigt
- ISSN: 1932-6203