Relationship of NADPH Oxidase-1 expression to beta cell dysfunction induced by inflammatory cytokines

Jessica Weaver; David A Taylor-Fishwick

doi:10.1016/j.bbrc.2017.02.089

Relationship of NADPH Oxidase-1 expression to beta cell dysfunction induced by inflammatory cytokines

Biochem Biophys Res Commun. 2017 Apr 1;485(2):290-294. doi: 10.1016/j.bbrc.2017.02.089. Epub 2017 Feb 21.

Authors

Jessica Weaver¹, David A Taylor-Fishwick²

Affiliations

¹ Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
² Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: taylord@evms.edu.

PMID: 28232183
DOI: 10.1016/j.bbrc.2017.02.089

Abstract

Redox stress related loss of beta cell function is a feature of diabetes. Exposure of beta cells and islets to inflammatory mediators elevates reactive oxygen species (ROS) and beta cell dysfunction. Direct molecular manipulation of NADPH oxidase-1 (NOX-1) has identified a key role for NOX-1 in cytokine-induced beta cell dysfunction. Plasmid driven elevation of NOX-1 resulted in elevated ROS, loss of glucose-stimulated-insulin-secretion and increased apoptosis. These outcomes on beta cell function are analogous to cytokine treatment. In contrast, reduction of NOX-1 expression, by shRNA, conferred protection to beta cells and islets from the damaging effects of inflammatory cytokines. Collectively, these data support the therapeutic potential for NOX-1 inhibition in diabetes.

Keywords: Beta cell function; Diabetes; Inflammation; NADPH oxidase; Protein expression; Reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
Cell Line
Cytokines / immunology*
Diabetes Mellitus / genetics
Diabetes Mellitus / immunology
Diabetes Mellitus / metabolism
Diabetes Mellitus / pathology
Glucose / metabolism
Inflammation / genetics
Inflammation / immunology*
Inflammation / metabolism
Inflammation / pathology
Insulin / metabolism
Insulin-Secreting Cells / cytology
Insulin-Secreting Cells / immunology*
Insulin-Secreting Cells / metabolism
Insulin-Secreting Cells / pathology*
Mice
NADH, NADPH Oxidoreductases / genetics
NADH, NADPH Oxidoreductases / immunology*
NADH, NADPH Oxidoreductases / metabolism
NADPH Oxidase 1
Oxidative Stress
RNA Interference
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Up-Regulation

Substances

Cytokines
Insulin
RNA, Small Interfering
Reactive Oxygen Species
NADH, NADPH Oxidoreductases
NADPH Oxidase 1
Glucose