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Glucose-Dependent G...
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Gandasi, Nikhil RUppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
(author)
Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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Elsevier BV,2018
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Numbers
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LIBRIS-ID:oai:DiVA.org:uu-341518
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-341518URI
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https://doi.org/10.1016/j.cmet.2017.12.017DOI
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https://lup.lub.lu.se/record/fdad7259-5fec-46ec-b498-ce63a7581163URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Glucose-stimulated insulin secretion is biphasic, with a rapid first phase and a slowly developing sustained second phase; both are disturbed in type 2 diabetes (T2D). Biphasic secretion results from vastly different release probabilities of individual insulin granules, but the morphological and molecular basis for this is unclear. Here, we show that human insulin secretion and exocytosis critically depend on the availability of membrane-docked granules and that T2D is associated with a strong reduction in granule docking. Glucose accelerated granule docking, and this effect was absent in T2D. Newly docked granules only slowly acquired release competence; this was regulated by major signaling pathways, but not glucose. Gene expression analysis indicated that key proteins involved in granule docking are downregulated in T2D, and overexpression of these proteins increased granule docking. The findings establish granule docking as an important glucose-dependent step in human insulin secretion that is dysregulated in T2D.
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Yin, Peng,1982-Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)yinyi639
(author)
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Omar-Hmeadi, MuhmmadUppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)muhhm810
(author)
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Ottosson Laakso, EmiliaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-eo_
(author)
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Vikman, PetterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)wbl-pwi
(author)
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Barg, Sebastian,1969-Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:lu)mphy-sba
(author)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Related titles
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In:Cell Metabolism: Elsevier BV27:2, s. 470-4781550-41311932-7420
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