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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Her, Tracy K.
in Cooperation with on an Cooperation-Score of 37%
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Publications (2/2 displayed)
- 2021178-OR: Lipotoxicity Stimulates ß-Cell Extracellular Vesicle Secretion Which Induces ß-Cell Dysfunction and Perturbs ß-Cell Transcriptional Identity
- 2019199-OR: Time-Restricted Feeding Ameliorates Metabolic Dysfunction through the Restoration of Circadian Beta-Cell Function and Transcriptional Identity
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article
199-OR: Time-Restricted Feeding Ameliorates Metabolic Dysfunction through the Restoration of Circadian Beta-Cell Function and Transcriptional Identity
Abstract
<jats:p>There are clear associations between circadian disruption (CD), induction of pancreatic β-cell failure and T2DM. However, the underlying mechanisms driving these associations remain unclear. CD is behaviorally characterized by the dysregulation of circadian feeding patterns, which play a key role in the regulation of glucose homeostasis. Therefore, we set out to test the hypothesis that disrupted circadian feeding patterns mediate CD-induced metabolic dysfunction by promoting β-cell failure and reprogramming of the circadian islet transcriptome. To address this, C57B6 mice were assigned into 3 protocols for 12 weeks: 1) LD: exposed to standard light-dark cycle on ad libitum chow; 2) CD: Constant light exposure, to disrupt endogenous circadian rhythms, on ad libitum chow; 3) CD-tRF: Constant light exposure with time-restricted access to chow (tRF) during the first 8h of the circadian “active/feeding” phase. CD led to a loss of circadian rhythmicity in feeding, activity and energy expenditure (p&lt;0.05 vs. LD). These behavioral abnormalities corresponded with loss of circadian regulation of glucose tolerance and insulin response (p&lt;0.05 vs. LD). Moreover, time-dependent RNA-seq of islets revealed that CD significantly altered 98% of genes that were differentially expressed under LD conditions. Restoration of circadian feeding patterns (without altering daily energy intake) in CD-tRF led to reversal of metabolic defects by enhancing circadian glucose tolerance and insulin secretory response (p&lt;0.05 vs. CD). Importantly, CD-tRF normalized circadian expression patterns of 707 genes enriched for KEGG pathways regulating key aspects of β-cell function such as insulin secretion, protein processing in ER, and NF-kB signaling (all FDR&lt;0.05). This study suggests that the deleterious metabolic effects of CD on the β-cell are a consequence of disrupted circadian feeding patterns and imply that tRF may attenuate β-cell failure in T2DM.</jats:p><jats:sec><jats:title>Disclosure</jats:title><jats:p>M. Brown: None. T.K. Her: None. A. Matveyenko: None.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>National Institutes of Health (R01DK98468)</jats:p></jats:sec>