Cross-Organ Regulation of Glucose Homeostasis Under Metabolic Stress

Glucose homeostasis depends on coordinated signaling among the endocrine pancreas, liver, skeletal muscle, adipose tissue, gut, vasculature, and central neuroendocrine circuits. Under physiological conditions these systems adapt continuously to feeding, fasting, exercise, circadian timing, reproductive state, and environmental cues to preserve metabolic balance. Under metabolic stress this coordination breaks down. Chronic nutrient excess, insulin resistance, inflammation, and altered hormonal signaling place sustained demand on both insulin-secreting and insulin-responsive tissues, driving progressive dysfunction across organs.Recent work has identified several mechanisms behind this transition, including altered calcium signaling, impaired stimulus-secretion coupling, mitochondrial dysfunction, endoplasmic reticulum stress, redox imbalance, inflammatory signaling, and loss of cellular identity or plasticity in metabolically active tissues. In parallel, autonomic and neuroendocrine pathways and direct tissue-to-tissue communication are emerging as central organizers of whole-body glucose regulation.Yet most of these processes are still studied in isolation. The field lacks an integrative framework that connects molecular and cellular events to tissue crosstalk and organism-level metabolic phenotypes. Bridging these scales is the central challenge this Research Topic addresses.Aim This Research Topic brings together mechanistic studies on how metabolic stress reshapes communication among the brain, pancreatic islets, liver, skeletal muscle, adipose tissue, gut, and vasculature to alter glucose homeostasis. We particularly welcome work that bridges levels of organization, from channels, transporters, signaling pathways, and cellular stress responses through to inter-organ regulation and whole-body metabolic function.Scope of submissions Contributions may address cellular, tissue, animal, or human physiology. Clinical and translational studies are encouraged when they remain grounded in metabolic mechanisms and cross-organ regulation. We are especially interested in work that clarifies why compensatory responses fail and how dysfunction propagates across organs in obesity, insulin resistance, prediabetes, and diabetes.Themes of interest include, but are not limited to:1. Neural, neuroendocrine, and autonomic control of glucose homeostasis, including central regulation of feeding, insulin secretion, hepatic glucose output, and counter-regulation2. Hepatic, skeletal muscle, and adipose determinants of glucose regulation, including insulin signaling, glucose uptake, substrate partitioning, metabolic flexibility, and systemic insulin resistance3. Gut-derived regulation, including nutrient sensing, incretin biology, microbiota-related signaling, and gut-brain, gut-liver, and gut-pancreas communication4. Cross-organ coordination, including liver-muscle, adipose-brain, brain-pancreas, vascular-islet, and islet-immune interactions5. Cellular heterogeneity, plasticity, and dysfunction, including nutrient sensing and stress responses in metabolically active cells6. Mitochondrial, redox, ER stress, autophagy-related, and inflammatory mechanisms that link cellular stress to whole-body glucose dysregulation7. Physiological modifiers of glucose control, including sex, aging, circadian timing, exercise, fasting, nutrient timing, and environmental stressors8. Integrative and translational approaches that combine mechanistic insight with imaging, omics, metabolomics, computational modeling, or network analysis Topic editors: Dario C Ramirez Source: https://www.frontiersin.org/research-topics/83354/cross-organ-regulation-of-glucose-homeostasis-under-metabolic-stress