ArticlePloS one2013
Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 76 citations in OpenAlex.
- Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome.PloS one · 2014Trial
- The dawn phenomenon in diabetes: pathophysiology from periphery to central nervous system and circadian rhythm-based therapeutic strategies.Acta diabetologica · 2026Review
- Clock genes in pancreatic disease progression: from circadian regulation to dysfunction.Annals of medicine · 2025Review
- Nuclear receptor protein: REV-ERB.Northern clinics of Istanbul · 2025Review
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Review
- Exploring the Effects of Metabolism-Disrupting Chemicals on Pancreatic α-Cell Viability, Gene Expression and Function: A Screening Testing Approach.International journal of molecular sciences · 2023Article
- Screening of Metabolism-Disrupting Chemicals on Pancreatic α-Cells Using In Vitro Methods.International journal of molecular sciences · 2022Article
- The Role of Circadian Clock Genes in Critical Illness: The Potential Role of Translational Clock Gene Therapies for Targeting Inflammation, Mitochondrial Function, and Muscle Mass in Intensive Care.Journal of biological rhythms · 2022Review
- A trio of biological rhythms and their relevance in rhythmic mechanical stimulation of cell cultures.Frontiers in psychology · 2022Article
- "Shedding Light on Light": A Review on the Effects on Mental Health of Exposure to Optical Radiation.International journal of environmental research and public health · 2021Review
- Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock.General and comparative endocrinology · 2021Review
- Clock Genes, Inflammation and the Immune System-Implications for Diabetes, Obesity and Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm.Nutrients · 2020Review
- Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?Journal of clinical medicine · 2020Article
- Time-of-Day Effects on Short-Duration Maximal Exercise Performance.Scientific reports · 2020Review
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
- Targeting REV-ERBα for therapeutic purposes: promises and challenges.Theranostics · 2020Review
- The effect of diurnal variation on the performance of exhaustive continuous and alternated-intensity cycling exercises.PloS one · 2020Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60-70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.