uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
High extracellular glucose inhibits exocytosis through disruption of syntaxin 1A-containing lipid rafts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. (Sebastian Barg)
Show others and affiliations
2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 389, no 2, 241-246 p.Article in journal (Refereed) Published
Abstract [en]

Diabetes is characterized by high blood glucose which eventually impairs the secretion of insulin. Glucose directly affects cholesterol biosynthesis and may in turn affect cellular structures that depend on the sterol, including lipid rafts that help organize the secretory apparatus. Here, we investigated the long-term effects of glucose upon lipid rafts and secretory granule dynamics in pancreatic beta-cells. Raft fractions, identified by the presence of GM1 and flotillin, contained characteristically high levels of cholesterol and syntaxin 1A, the t-SNARE which tethers granules to the plasma membrane. Seventy-two hours exposure to 28mM glucose resulted in approximately 30% reduction in membrane cholesterol, with consequent redistribution of raft markers and syntaxin 1A throughout the plasma membrane. Live cell imaging indicated loss of syntaxin 1A from granule docking sites, and fewer docked granules. In conclusion, glucose-mediated inhibition of cholesterol biosynthesis perturbs lipid raft stability, resulting in a loss of syntaxin 1A from granule docking sites and inhibition of insulin secretion.

Place, publisher, year, edition, pages
2009. Vol. 389, no 2, 241-246 p.
Keyword [en]
Hyperglycemia, Cholesterol, Insulin secretion, SNAREs
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-119547DOI: 10.1016/j.bbrc.2009.08.126ISI: 000270764400007PubMedID: 19716806OAI: oai:DiVA.org:uu-119547DiVA: diva2:300466
Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2011-11-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Barg, Sebastian
By organisation
Department of Medical Cell Biology
In the same journal
Biochemical and Biophysical Research Communications - BBRC
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 250 hits
ReferencesLink to record
Permanent link

Direct link