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Clock genes dysregulation modifies the redox state of pancreatic β cell and modulates glucose stimulated insulin secretion via NADPH oxidase.

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Author(s):
Daniel Simões de Jesus
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Angelo Rafael Carpinelli; Rui Curi; Rodrigo Antonio Peliciari Garcia; Francisco Rafael Martins Laurindo; Lucia Rossetti Lopes
Advisor: Angelo Rafael Carpinelli
Abstract

Clock genes are responsible for homeostasis and circadian rhythm in various biological systems, including endocrine pancreas. In β -cells, they are important for the regulation of metabolism and insulin secretion (IS), and its absence can lead to development of diabetes. NADPH oxidase (NOX) is an enzymatic complex responsible for production of superoxide anion by reducing molecular oxygen. In pancreatic islets, NOX regulates glucose metabolism and IS through modulation of the intracellular redox state. The aim of our study was to investigate whether dysregulation of clock genes mediated by Bmal1 suppression would be able to modulate NOX activity and redox state in pancreatic β cells, thus influencing the SI. In this work, the lack of Bmal1 altered the activity and expression of NOX, deregulating the intracellular redox state. These changes led to reduced cell viability and changes in cell response after stimulation with glucose, resulting in a deficiency in β cell main function, GSIS. (AU)

FAPESP's process: 11/08172-0 - Participation of clock genes in the insulin secretion process in BRIN-BD11 cell line
Grantee:Daniel Simões de Jesus
Support Opportunities: Scholarships in Brazil - Doctorate