ArticleMetabolites2026
Diurnal Insulin Clearance and Circadian Metabolic Gene Signatures in MASLD: Integrative Multi-Dataset Physiological and Transcriptomic Analysis.
Article in Metabolites, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
objectivesInsulin clearance is a key determinant of circulating insulin availability, but its diurnal variation and relationship with circadian metabolic programs in metabolic dysfunction associated steatotic liver disease (MASLD) remain unclear. This study aimed to explore diurnal insulin clearance in humans and examine associated metabolic gene signatures in MASLD.
methodsA single-subject pilot assessment was performed to explore daytime-nighttime differences in insulin clearance rate (ICR) surrogate index, followed by evaluation using public hyperinsulinemic-euglycemic clamp datasets from healthy individuals and patients with MASLD. Public circadian transcriptomic datasets, spatial transcriptomic data, and a time course high-fat diet (HFD)-induced mouse dataset were integrated. A predefined panel of insulin clearance-related and circadian genes, including carcinoembryonic antigen-related cell adhesion molecule 1 (
resultsThe pilot assessment showed higher nighttime than daytime ICR, and independent clamp datasets showed a similar pattern in healthy individuals. In MASLD, nighttime ICR remained relatively higher, whereas overall insulin clearance was reduced compared with controls. Human blood-based circadian transcriptomic datasets identified rhythmic expression patterns of selected genes involved in insulin clearance and circadian regulation, including
conclusionsThese integrative findings suggest that insulin clearance may exhibit diurnal variation and may be linked to circadian metabolic gene signatures across systemic and hepatic datasets in MASLD. Larger controlled human studies are needed to validate the temporal regulation of insulin clearance and its metabolic relevance.
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