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3-Deoxyglucosone interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in the enteroendocrine L cell line STC-1.

Abstract：

:Maintenance of glucose homeostasis is reciprocally regulated by insulin and glucagon-like peptide-1 (GLP-1). We previously reported that GLP-1 secretion in response to an oral glucose load was impaired following an administration of 3-deoxyglucosone (3DG), an independent factor associated with the development of pre-diabetes. Here we investigated the effects of 3DG on insulin signaling and insulin-induced GLP-1 secretion under high-glucose conditions in the enteroendocrine L cell line STC-1. STC-1 cells were exposed to 3DG (80, 300, and 1000 ng/ml) in the presence of 10-7 M insulin and 25 mM glucose. GLP-1 secretion was determined by ELISA, glucose uptake was monitored with 2-NBDG (2-(N(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose), glucose consumption was detected by glucoseoxidase, and protein expression of insulin signaling molecules was examined by western blot. Results showed a decrease in insulin-induced GLP-1 secretion and insulin receptor phosphorylation after 3DG treatment. Concomitantly, 3DG treatment inhibited insulin-induced phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway activation. In the presence, but not absence, of insulin, 3DG treatment decreased insulin-stimulated glucose consumption. Inhibition of PI3K with Wortmannin attenuated insulin-induced increment in glucose transporter 2 (GLUT2) expression and 2-NBDG uptake. Accordingly, insulin-induced increase in GLUT2 expression and 2-NBGD uptake was significantly inhibited by 3DG treatment. 3DG-mediated reduction in GLUT2 expression contributes to the attenuation of insulin-induced GLP-1 secretion under high-glucose conditions in part through the insulin-PI3K/Akt/GLUT2 pathway in STC-1 cells. We conclude that 3DG interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in STC-1 cells.

journal_name

Mol Biol Rep

journal_title

Molecular biology reports

authors

Song X,Zhou L,Xu H,Wang F,Liang G,Zhang L,Huang F,Jiang G

doi

10.1007/s11033-019-04926-0

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

4799-4808

issue

eissn

0301-4851

issn

1573-4978

pii

10.1007/s11033-019-04926-0

journal_volume

pub_type

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3-Deoxyglucosone interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in the enteroendocrine L cell line STC-1.