ArticleDiabetes & vascular disease research
Hyperinsulinemia alters insulin receptor presentation and internalization in brain microvascular endothelial cells.
Article in Diabetes & vascular disease research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Effect of a single exercise bout on fasting cerebral blood flow and brain insulin sensitivity in middle-aged to older adults.Experimental physiology · 2026Article
- Immunometabolism Reframes Alzheimer's Disease: From Systemic Dysmetabolism to Glial Rewiring.Cellular and molecular neurobiology · 2026Review
- Feto-placental endothelial cells of female neonates are more susceptible to gestational diabetes-induced changes.Histochemistry and cell biology · 2025Article
- Adipokines at the Metabolic-Brain Interface: Therapeutic Modulation by Antidiabetic Agents and Natural Compounds in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- Insulin Resistance, a Risk Factor for Alzheimer's Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach.Biomedicines · 2024Review
- Sex Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.Journal of clinical medicine · 2024Article
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.International journal of molecular sciences · 2023Article
- Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses.Cell communication and signaling : CCS · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Insulin receptors are internalized by endothelial cells to facilitate their physiological processes; however, the impact of hyperinsulinemia in brain endothelial cells is not known. Thus, the aim of this study was to elucidate the impact hyperinsulinemia plays on insulin receptor internalization through changes in phosphorylation, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). Hippocampal microvessels were isolated from high-fat diet fed mice and assessed for insulin signaling activation, a process known to be involved with receptor internalization. Surface insulin receptors in brain microvascular endothelial cells were labelled to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without the PTP1B antagonist, Claramine. Our results indicated that insulin receptor levels increased in tandem with decreased receptor signaling in the high-fat diet mouse microvessels. Insulin receptors of cells subjected to hyperinsulinemic treatment demonstrate splice variation towards decreased IR-A mRNA expression and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling. Claramine restored signaling and receptor internalization in cells treated with hyperinsulinemia. In conclusion, hyperinsulinemia impacts brain microvascular endothelial cell insulin receptor signaling and internalization, likely via alternative splicing and increased negative feedback from PTP1B.
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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.