GSBS Student Publications

Title

Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1

Publication Date

2006-09-05

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Department of Medicine, Diabetes Division

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

In pancreatic beta cells, the endoplasmic reticulum (ER) is an important site for insulin biosynthesis and the folding of newly synthesized proinsulin. Here, we show that IRE1alpha, an ER-resident protein kinase, has a crucial function in insulin biosynthesis. IRE1alpha phosphorylation is coupled to insulin biosynthesis in response to transient exposure to high glucose; inactivation of IRE1alpha signaling by siRNA or inhibition of IRE1alpha phosphorylation hinders insulin biosynthesis. IRE1 activation by high glucose does not accompany XBP-1 splicing and BiP dissociation but upregulates its target genes such as WFS1. Thus, IRE1 signaling activated by transient exposure to high glucose uses a unique subset of downstream components and has a beneficial effect on pancreatic beta cells. In contrast, chronic exposure of beta cells to high glucose causes ER stress and hyperactivation of IRE1, leading to the suppression of insulin gene expression. IRE1 signaling is therefore a potential target for therapeutic regulation of insulin biosynthesis.

DOI of Published Version

10.1016/j.cmet.2006.07.007

Source

Cell Metab. 2006 Sep;4(3):245-54. Link to article on publisher's site

Journal/Book/Conference Title

Cell metabolism

Related Resources

Link to article in PubMed

PubMed ID

16950141

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