Mar 25, 2020

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis

BioRxiv : the Preprint Server for Biology
Gaelle R CarratGuy A Rutter

Abstract

Objective: Risk alleles for type 2 diabetes at the STARD10 locus are associated with lowered STARD10 expression in the β-cell, impaired glucose-induced insulin secretion and decreased circulating proinsulin:insulin ratios. Although likely to serve as a mediator of intracellular lipid transfer, the identity of the transported lipids, and thus the pathways through which STARD10 regulates β-cell function, are not understood. The aim of this study was to identify the lipids transported and affected by STARD10 in the beta-cell and its effect on proinsulin processing and insulin granule biogenesis and maturation. Methods: We used isolated islets from mice deleted selectively in the beta-cell for Stard10 (βStarD10KO) and performed electron microscopy, pulse-chase, RNA sequencing and lipidomic analyses. Proteomic analysis of STARD10 binding partners was executed in INS1 (832/13) cell line. X-ray crystallography followed by molecular docking and lipid overlay assay were performed on purified STARD10 protein. Results: βStarD10KO islets had a sharply altered dense core granule appearance, with a dramatic increase in the number of ″rod-like″ dense cores. Correspondingly, basal secretion of proinsulin was increased. Amongst the differential...Continue Reading

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Mentioned in this Paper

STARD10 gene
STARD10 protein, human
Laboratory mice
Measurement of Serum Lipid Level
FOXM1
Intracellular
Alleles
Phosphatidylinositols
Lipid-Linked Proteins
Cell Secretion

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