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In this study, Juan-Mateu et al. discover microexons that modulate insulin secretion in the pancreas in response to glucose levels in beta cell lines and mouse islets. Human genetic variants modulating these islet microexons are associated with type 2 diabetes risk.
Shin et al. gain structural insight into how pyrimidine synthesis is coupled to cell cycle regulation through the modulation of CAD activity, and identify allostery as a major means to regulate de novo pyrimidine biosynthesis during the mammalian cell cycle.
Dai et al. show that in response to low glucose levels, AMP-activated protein kinase-mediated phosphorylation of WDR24, a component of the GATOR2 complex, leads to suppression of mTORC1 activation.
Retinal pigment epithelial cells are identified as a local source of insulin in the retina, which is stimulated by phagocytosis of photoreceptor outer segments and starvation and has the potential to influence retinal physiology and disease.
Prolonged exposure to acid is shown to reprogram T cell intracellular methionine metabolism to preserve T cell stemness and increase anti-tumor efficacy.
Coral et al. characterize genetically determined discordance between obesity and type 2 diabetes, identifying discordant genes that may convey protection against type 2 diabetes in obesity.
The authors combine multi-layered omics with clinical and biochemical features from individuals affected with methylmalonic aciduria, a rare inherited disease affecting succinyl-CoA synthesis, revealing that anaplerotic rewiring is a targetable feature.
Kuang, Dou et al. show that upon Salmonella Typhimurium infection in mice, macrophages release extracellular vesicles (EVs) that harbor iron-uptake receptors. By sequestering iron via a humoral mechanism, these EVs limit bacterial growth and thereby protect against infection.
In this study, Oaks and Patel et al. characterize the crosstalk between the pentose phosphate pathway and mitochondrial redox homeostasis in the context of aldose reductase and transaldolase deficiency and the contribution of pentose phosphate pathway mitochondria deregulation to the progression from cirrhosis to hepatocellular carcinoma.
Xiao and Kennelly et al. show that Aster-mediated nonvesicular cholesterol transport in the liver regulates hepatic and systemic lipid homeostasis during fasting, as well as reverse cholesterol transport.
The authors show that caloric restriction increases the intestinal abundance of Bifidobacterium bifidum, which in turn blunts tumour development in mice.
Zhang et al. identify a unique population of cardiac-resident macrophages that could be a potential therapeutic strategy for sepsis-induced cardiomyopathy.
Yang, Yan, Ma et al. provide a comprehensive lactylome analysis of hepatocellular carcinoma patients, and show that analysis of protein lactylation can help uncover mechanisms that couple metabolic flux with metabolic alterations in hepatocellular carcinoma.
Grb10, an adaptor protein known to regulate insulin signalling, can interact with the leptin receptor for enhancement of leptin signalling in hypothalamic AgRP and POMC neurons in mice.