ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/066/SRR28602966/SRR28602966.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/068/SRR28602968/SRR28602968.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/071/SRR28602971/SRR28602971.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/070/SRR28602970/SRR28602970.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/067/SRR28602967/SRR28602967.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/072/SRR28602972/SRR28602972.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/073/SRR28602973/SRR28602973.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR286/069/SRR28602969/SRR28602969.fastq.gzprimary200OKGenomicsHistology & Embryology, University of Rijeka faculty of medicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA1098234Mus musculusxref:PubMed:38811816Viral infection makes us feel sick. The extent of these changes to our metabolism are relative to the severity of disease. Whether blood glucose levels are subject to infection-induced modulation is largely unknown. Here we show that strong, non-lethal infection restricts systemic glucose availability which promotes the antiviral IFN-I response. Following systemic viral infection of mice, we find that IFNγ produced by γδ T cells directly stimulates pancreatic β-cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous glucose output by the liver. Glucose restriction enhances type-I interferon production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, which explains why patients with metabolic disease are more susceptible to viral infection. Overall design: To investigater the impact of cytokines on gene transcription in pancreatc beta cells, we FACS-purified these cells, after which we stimulated them with glucose in presence or absence of IFNg and IL-1b. We then performed gene expression analysis using data obtained from RNA-seq of 4 biolgical replicates under two different conditions Comparative gene expression profiling analysis of RNA-seq data for pancreatic beta cells stimulated with glucose in the presence (IFNg/IL1b) or absence (control) of IFNg and IL1bENAfalseAn IFNg-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune responseAn IFNg-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response2025-09-242024-04-16PRJNA1098234GSE2635991009038811816