An autocrine insulin feedback loop maintains pancreatic β-cell 3-phosphorylated inositol lipids

Jia Yu, Per Olof Berggren, Christopher J. Barker

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Phosphatidylinositol 3-kinases (PI3Ks) have a central role in pancreatic β-cell function. Downstream events include the regulation of K ATP channel activity, insulin secretion, gene transcription, and cell survival. Fewer data are available on the 3-phosphorylated inositol lipids (3-PIs) that are the primary products of these kinases. We characterized these PI3K products in insulin-secreting HIT T15 cells and were able to demonstrate, for the first time the presence of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. We then showed that glucose can significantly increase PtdIns(3,4,5)P3, PtdIns(3,4)P2, and notably PtdIns(3,5)P2. We investigated the mechanism(s) whereby these molecules are generated under both basal and glucose-stimulated conditions. We postulated that insulin exocytosis could drive the rises in 3-PIs. In our experimental system, we could detect a rise in insulin secretion within 1 min of glucose stimulation, thus allowing the possibility that early rises in 3-PIs are regulated by secreted insulin. This was confirmed because blockade of the β-cell insulin receptor completely abrogated the glucose-mediated increase of all three lipids, driving their concentrations below basal levels. Using primary pancreatic islets and either blockade of the insulin receptor or antibodies to insulin, we verified that basal insulin secretion is responsible for the maintenance of 3-PIs. Therefore, autocrine insulin signaling, a feature compromised in diabetes, is essential to up-regulate both basal and glucose-stimulated levels of a vital family of second messengers that preserve and drive pancreatic β-cell function.

Original languageEnglish
Pages (from-to)2775-2784
Number of pages10
JournalMolecular Endocrinology
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Inositol
Insulin
Lipids
Glucose
Insulin Receptor
Phosphatidylinositol 3-Kinases
Autocrine Communication
Insulin Antibodies
Exocytosis
Second Messenger Systems
Islets of Langerhans
Cell Survival
Phosphotransferases
Up-Regulation
Adenosine Triphosphate
Maintenance
Genes
phosphatidylinositol 3,5-diphosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

An autocrine insulin feedback loop maintains pancreatic β-cell 3-phosphorylated inositol lipids. / Yu, Jia; Berggren, Per Olof; Barker, Christopher J.

In: Molecular Endocrinology, Vol. 21, No. 11, 01.11.2007, p. 2775-2784.

Research output: Contribution to journalArticle

Yu, Jia ; Berggren, Per Olof ; Barker, Christopher J. / An autocrine insulin feedback loop maintains pancreatic β-cell 3-phosphorylated inositol lipids. In: Molecular Endocrinology. 2007 ; Vol. 21, No. 11. pp. 2775-2784.
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