ArticleProceedings of the National Academy of Sciences of the United States of America2020
In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- Circadian rhythms in major depressive disorder: mechanistic insights and therapeutic frontiers.Annals of medicine · 2026Review
- Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.Life science alliance · 2026Article
- From pancreas and islet resources to diabetes insights.Diabetologia · 2026Review
- Disrupted renal clock and blood pressure rhythms in type 2 diabetic nephropathy.Clinical science (London, England : 1979) · 2026Article
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Dual roles of circadian clock proteins in development and adult homeostasis.Npj biological timing and sleep · 2026Review
- Clock genes in pancreatic disease progression: from circadian regulation to dysfunction.Annals of medicine · 2025Review
- Potential and Mechanism of Nobiletin in Diabetes Mellitus and Associated Complications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of circadian CLOCK signaling in cellular senescence.Biogerontology · 2025Review
- Article
- Exploring nonlinear phenomena in animal vocalizations through oscillator theory.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Gut microbiota heterogeneity in non-alcoholic fatty liver disease: a narrative review of drivers, mechanisms, and clinical relevance.Frontiers in microbiology · 2025Review
- Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance.The Journal of physiology · 2024Article
- Core circadian transcription factor Bmal1 mediates β cell response and recovery from pro-inflammatory injury.iScience · 2024Article
- Article
- Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects.Life (Basel, Switzerland) · 2024Review
- MITOCHONDRIA-ASSOCIATED MEMBRANES ARE NOT ALTERED IN IMMUNE CELLS IN T2D.bioRxiv : the preprint server for biology · 2024Article
- Review
- Circadian organization of lipid landscape is perturbed in type 2 diabetic patients.Cell reports. Medicine · 2023Article
- Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology.Nature reviews. Gastroenterology & hepatology · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian clocks operative in pancreatic islets participate in the regulation of insulin secretion in humans and, if compromised, in the development of type 2 diabetes (T2D) in rodents. Here we demonstrate that human islet α- and β-cells that bear attenuated clocks exhibit strongly disrupted insulin and glucagon granule docking and exocytosis. To examine whether compromised clocks play a role in the pathogenesis of T2D in humans, we quantified parameters of molecular clocks operative in human T2D islets at population, single islet, and single islet cell levels. Strikingly, our experiments reveal that islets from T2D patients contain clocks with diminished circadian amplitudes and reduced in vitro synchronization capacity compared to their nondiabetic counterparts. Moreover, our data suggest that islet clocks orchestrate temporal profiles of insulin and glucagon secretion in a physiological context. This regulation was disrupted in T2D subjects, implying a role for the islet cell-autonomous clocks in T2D progression. Finally, Nobiletin, an agonist of the core-clock proteins RORα/γ, boosted both circadian amplitude of T2D islet clocks and insulin secretion by these islets. Our study emphasizes a link between the circadian clockwork and T2D and proposes that clock modulators hold promise as putative therapeutic agents for this frequent disorder.
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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.