Journal article
BMAL1 modulates ROS generation and insulin secretion in pancreatic β-cells: An effect possibly mediated via NOX2
Molecular and Cellular Endocrinology, Vol.555, pp.1-8
15/09/2022
Appears in Recent Faculty of Health Publications
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Abstract
The pancreatic β cells circadian clock plays a relevant role in glucose metabolism. NADPH oxidase (NOX) family is responsible for producing reactive oxygen species (ROS), such as superoxide anion and hydrogen peroxide, using NADPH as an electron donor. In pancreatic β-cells, NOX-derived ROS inhibits basal and glucose-stimulated insulin secretion. Thus, we hypothesized that the absence of BMAL1, a core circadian clock component, could trigger an increase of NOX2-derived ROS in pancreatic β cells, inhibiting insulin secretion under basal and stimulated glucose conditions. To test such hypothesis, Bmal1 knockdown (KD) was performed in cultured clonal β-cell line (INS-1E) and knocked out in isolated pancreatic islets, using a tissue-specific β-cells Bmal1 knockout (KO) mice. The insulin secretion was assessed in the presence of NOX inhibitors. The Bmal1 KD within INS-1E cells elicited a rise of intracellular ROS content under both glucose stimuli (2.8 mM and 16.7 mM), associated with an increase in Nox2 expression. Additionally, alterations of glutathione levels, CuZnSOD and catalase activities , reduction of ATP/ADP ratio, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aconitase activities , followed by glucokinase and Slc2a2 (Glut2) expression were also observed in INS-1E β-cells, reflecting in a diminished insulin secretion pattern. The isolated islets from β-cell Bmal1 / mice have shown a similar cellular response, where an increased NOX2-derived ROS content and a reduced basal-and glucose-stimulated insulin secretion were observed. Therefore, together with NOX inhibition (Apocynin), polyethene-glycol linked to superoxide dismutase (PEG-SOD), phorbol myristate acetate (PMA), and diethyldithiocarbamate (DDC) data, our findings suggest a possible BMAL1-mediated NOX2-derived ROS generation in pancreatic β cells, leading to the modulation of both basal-and glucose-stimulated insulin secretion.
Details
- Title
- BMAL1 modulates ROS generation and insulin secretion in pancreatic β-cells: An effect possibly mediated via NOX2
- Creators
- Daniel Simoes de Jesus (Author) - Federal University of Sao PauloPaula Bargi-Souza (Author)Vinicius Cruzat (Author) - Torrens UniversityVijay Yechoor (Author) - University of PittsburghAngelo Rafael Carpinelli (Author) - University of Sao PauloRodrigo Antonio Peliciari-Garcia (Author) - Federal University of Sao Paulo
- Publication Details
- Molecular and Cellular Endocrinology, Vol.555, pp.1-8
- Publisher
- Elsevier
- Grant note
- This research was supported by the Sao Paulo Research Foundation (FAPESP) (DSJ#2013/08769–1), Brazilian National Council for Scientific and Technological Development (CNPq; PB-S and RAP-G: 403972/2021–3) and Coordination for the Improvement of Higher Education Personnel (CAPES) (ARC).
- Identifiers
- 991013071413502368
- Copyright
- © 2022 Elsevier B.V. All rights reserved.
- Academic Unit
- Faculty of Health
- Language
- English
- Resource Type
- Journal article