ArticleProceedings of the National Academy of Sciences of the United States of America2017
Endothelial insulin receptors differentially control insulin signaling kinetics in peripheral tissues and brain of mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 129 citations in OpenAlex.
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- Contrast enhanced ultrasound and laser doppler flowmetry capture distinct aspects of tissue microvascular perfusion in nonhuman primates.Physiological reports · 2026Article
- Blood-brain barrier water permeability is elevated in type 2 diabetes and obesity: associations with cognitive function and metabolic markers.Fluids and barriers of the CNS · 2026Article
- Palmitoylation calibrates mitochondrial transport of insulin across the endothelium in insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Light-activated insulin receptor modulates neuronal plasticity and cerebellar-driven behavior.iScience · 2026Article
- Blood-Brain Barrier Permeability Is Elevated in Type 2 Diabetes and Obesity: Associations with Cognitive Function and Metabolic Markers.Research square · 2026Article
- Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.Brain, behavior, and immunity · 2026Article
- From oversight to insight: the curious case of the endothelial insulin receptor.Blood vessels, thrombosis & hemostasis · 2026Review
- Expanding the understanding of insulin resistance in brain and periphery.Trends in endocrinology and metabolism: TEM · 2026Review
- Article
- Central cytometabolic functional vascular coupling in health and disease.npj metabolic health and disease · 2025Review
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Maternal Gestational Diabetes Impairs Fetoplacental Insulin-Induced Vasodilation via AKT/eNOS Pathway and Reduces Placental Efficiency.International journal of molecular sciences · 2025Article
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Role of membrane microdomains in cardiac protection: strategies for diabetic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.Acta physiologica (Oxford, England) · 2025Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin receptors (IRs) on endothelial cells may have a role in the regulation of transport of circulating insulin to its target tissues; however, how this impacts on insulin action in vivo is unclear. Using mice with endothelial-specific inactivation of the IR gene (EndoIRKO), we find that in response to systemic insulin stimulation, loss of endothelial IRs caused delayed onset of insulin signaling in skeletal muscle, brown fat, hypothalamus, hippocampus, and prefrontal cortex but not in liver or olfactory bulb. At the level of the brain, the delay of insulin signaling was associated with decreased levels of hypothalamic proopiomelanocortin, leading to increased food intake and obesity accompanied with hyperinsulinemia and hyperleptinemia. The loss of endothelial IRs also resulted in a delay in the acute hypoglycemic effect of systemic insulin administration and impaired glucose tolerance. In high-fat diet-treated mice, knockout of the endothelial IRs accelerated development of systemic insulin resistance but not food intake and obesity. Thus, IRs on endothelial cells have an important role in transendothelial insulin delivery in vivo which differentially regulates the kinetics of insulin signaling and insulin action in peripheral target tissues and different brain regions. Loss of this function predisposes animals to systemic insulin resistance, overeating, and obesity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.