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Interleukin-10 promotes the formation of microcirculatory defects in the brain associated with cognitive impairment in a mouse model of type 1 diabetes.
In Greenlandic Inuit, a TBC1D4 loss-of-function mutation increases type 2 diabetes risk by tenfold. Carriers show severe muscle insulin resistance, impaired glucose disposal and reduced muscle GLUT4, yet exercise mitigates these defects, offering potential for personalized lifestyle interventions.
Branched-chain α-ketoacids are shown to aerobically activate HIF1α signalling, which induces a phenotypic switch in vascular smooth muscle cells that is potentially relevant in the context of pulmonary artery hypertension.
Malik, Guo et al. show that Ntrk2/Trkb-mediated neurotrophic signalling regulates dopamine levels by controlling glutathioneâascorbate metabolism, thus impacting striatal dopaminergic circuits and motor function
The mevalonate pathway intermediate farnesyl pyrophosphate is shown to regulate the survival of migratory dendritic cells by affecting their mitochondrial metabolism, thereby contributing to the pathogenesis of systemic lupus erythematosus.
In a genome-wide association study for traits related to pancreatic beta-cell function in 26,000 individuals, 55 independent associations mapping to 44 genetic loci are identified.
OâCarroll and Peace et al. provide a mechanism for the induction of type I interferons by the immunomodulatory compound itaconate, which involves inhibition of succinate dehydrogenase and release of mitochondrial double-stranded RNA.
Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.
Genetic and pharmacological inhibition of the overproduction of oxalate in the liver alleviates metabolic dysfunction-associated steatohepatitis in male mice.
The authors systematically study biological influences on the human plasma proteome in a large cohort, thereby revealing causal associations between plasma proteins and modifiable risk factors for proteinâdisease associations.
LXRα is highly expressed in hepatocytes, where it regulates cholesterol abundance and stimulates lipogenesis. The authors provide evidence in humans and mice that impaired LXRα signalling is hepatotoxic, despite its potent lipogenic actions.
Oral administration of the anti-diabetic drug acarbose is shown to enhance the efficacy of cancer anti-PD-1 immunotherapy in female mice by modulating the composition and metabolism of the gut microbiota.
Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.
Impaired somatostatin secretion owing to loss of β- to δ-cell electrical coupling underlies defective counter-regulatory glucagon secretion in type-1 diabetes.
Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.
Adults with overweight or obesity who exercise regularly for at least 2âyears exhibit distinct structural and proteomic characteristics in abdominal subcutaneous adipose tissue that may contribute to better cardiometabolic health outcomes.
Buglakova et al. present 13C-SpaceM, a method that combines stable isotope tracing with imaging mass spectrometry thus enabling spatial analysis of lipid dynamics with near-single-cell resolution in tissues.
