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Glucose-Dependent G...
Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
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- Gandasi, Nikhil R (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Yin, Peng, 1982- (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Omar-Hmeadi, Muhmmad (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Ottosson Laakso, Emilia (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Vikman, Petter (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Barg, Sebastian, 1969- (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- Engelska.
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:2, s. 470-478
- Relaterad länk:
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http://www.cell.com/...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- GLP-1
- biphasic secretion
- dense core vesicle
- docking
- exocytosis
- genome-wide association
- insulin secretion
- priming
- somatostatin
- type 2 diabetes
- biphasic secretion
- dense core vesicle
- docking
- exocytosis
- genome-wide association
- GLP-1
- insulin secretion
- priming
- somatostatin
- type 2 diabetes
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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