Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity

Chia Wei Lin, Feifei Yan, Satoko Shimamura, Sebastian Barg, Show-Ling Shyng

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

ATP-sensitive K+ channels (KATP channels) of pancreatic β-cells play key roles in glucose-stimulated insulin secretion by linking metabolic signals to cell excitability. Membrane phosphoinositides, in particular phosphatidylinositol 4,5-bisphosphates (PIP2), stimulate KATP 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 β-cells. Here, we tested this hypothesis by manipulating the interactions between KATP channels and membrane phospholipids in a β-cell line, INS-1, and assessing how the manipulations affect membrane excitability and insulin secretion. We demonstrate that disruption of channel interactions with PIP2 by overexpressing PIP2-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 PIP2 levels via overexpression of a lipid kinase, phosphatidylinositol 4-phosphate 5 kinase, decreases the ATP sensitivity of endogenous KATP channels by ∼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 KATP channels in regulating insulin secretion.

Original languageEnglish (US)
Pages (from-to)2852-2858
Number of pages7
JournalDiabetes
Volume54
Issue number10
DOIs
StatePublished - Oct 2005

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KATP Channels
Phosphatidylinositols
Adenosine Triphosphate
Insulin
Membranes
Glucose
Ion Channels
Phospholipids
Phosphotransferases
Lipids
Cell Line

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity. / Lin, Chia Wei; Yan, Feifei; Shimamura, Satoko; Barg, Sebastian; Shyng, Show-Ling.

In: Diabetes, Vol. 54, No. 10, 10.2005, p. 2852-2858.

Research output: Contribution to journalArticle

Lin, Chia Wei ; Yan, Feifei ; Shimamura, Satoko ; Barg, Sebastian ; Shyng, Show-Ling. / Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity. In: Diabetes. 2005 ; Vol. 54, No. 10. pp. 2852-2858.
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