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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity.
Show others and affiliations
2005 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, no 10, 2852-8 p.Article in journal (Refereed) Published
Abstract [en]

ATP-sensitive K(+) channels (K(ATP) channels) of pancreatic beta-cells play key roles in glucose-stimulated insulin secretion by linking metabolic signals to cell excitability. Membrane phosphoinositides, in particular phosphatidylinositol 4,5-bisphosphates (PIP(2)), stimulate K(ATP) channels and decrease channel sensitivity to ATP inhibition; as such, they have been postulated as critical regulators of K(ATP) channels and hence of insulin secretion in beta-cells. Here, we tested this hypothesis by manipulating the interactions between K(ATP) channels and membrane phospholipids in a beta-cell line, INS-1, and assessing how the manipulations affect membrane excitability and insulin secretion. We demonstrate that disruption of channel interactions with PIP(2) by overexpressing PIP(2)-insensitive channel subunits leads to membrane depolarization and elevated basal level insulin secretion at low glucose concentrations. By contrast, facilitation of channel interactions with PIP(2) by upregulating PIP(2) levels via overexpression of a lipid kinase, phosphatidylinositol 4-phosphate 5 kinase, decreases the ATP sensitivity of endogenous K(ATP) channels by approximately 26-fold and renders INS-1 cells hyperpolarized, unable to secrete insulin properly in the face of high glucose. Our results establish an important role of the interaction between membrane phosphoinositides and K(ATP) channels in regulating insulin secretion.

Place, publisher, year, edition, pages
2005. Vol. 54, no 10, 2852-8 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-161863PubMedID: 16186385OAI: oai:DiVA.org:uu-161863DiVA: diva2:457792
Available from: 2011-11-19 Created: 2011-11-19 Last updated: 2017-12-08

Open Access in DiVA

No full text

PubMed

Authority records BETA

Barg, Sebastian

Search in DiVA

By author/editor
Barg, Sebastian
In the same journal
Diabetes
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

pubmed
urn-nbn

Altmetric score

pubmed
urn-nbn
Total: 630 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf