ArticleAmerican journal of physiology. Heart and circulatory physiology2019
Persistent insulin signaling coupled with restricted PI3K activation causes insulin-induced vasoconstriction.
Article in American journal of physiology. Heart and circulatory physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- [A prospectively randomized controlled study of the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients].Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns · 2021Trial
- Resistance exercise breaks during prolonged sitting augment the blood flow response to a subsequent oral glucose load in sedentary adults.Experimental physiology · 2026Article
- Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- Repurposing Antidiabetic Drugs for Cerebrovascular Diseases: Causal Evidence from Drug Target Mendelian Randomization and Colocalization.Molecular neurobiology · 2025Article
- The metabolically protective energy expenditure increase ofAmerican journal of physiology. Endocrinology and metabolism · 2025Article
- Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes.The Journal of clinical endocrinology and metabolism · 2025Article
- Skeletal muscle microvascular hemodynamic responses during hyperinsulinemic-euglycemic clamp in a Zucker Diabetic Sprague Dawley rat model of type 2 diabetes.Frontiers in physiology · 2025Article
- Impact of sex and diet-induced weight loss on vascular insulin sensitivity in type 2 diabetes.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- New insights into mechanisms of endothelial insulin resistance in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2022Review
- Young Women Are Protected Against Vascular Insulin Resistance Induced by Adoption of an Obesogenic Lifestyle.Endocrinology · 2022Article
- Role of the Autonomic Nervous System in the Hemodynamic Response to Hyperinsulinemia-Implications for Obesity and Insulin Resistance.Current diabetes reports · 2022Review
- Role of Endothelin-1 Receptors in Limiting Leg Blood Flow and Glucose Uptake During Hyperinsulinemia in Type 2 Diabetes.Endocrinology · 2022Article
- Sevoflurane and isoflurane inhibit KCl-induced, Rho kinase-mediated, and PI3K-participated vasoconstriction in aged diabetic rat aortas.BMC anesthesiology · 2021Article
- Antidiabetic compounds 8a, 8b, 8k, and 9h enhance insulin secretion: activity and mechanism.Endocrine · 2021Article
- Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer's Disease.Frontiers in molecular biosciences · 2021Review
- Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling.American journal of physiology. Endocrinology and metabolism · 2020 · on this mapArticle
- A Protein/Lipid Preload Attenuates Glucose-Induced Endothelial Dysfunction in Individuals with Abnormal Glucose Tolerance.Nutrients · 2020Article
- Sympathetically mediated increases in cardiac output, not restraint of peripheral vasodilation, contribute to blood pressure maintenance during hyperinsulinemia.American journal of physiology. Heart and circulatory physiology · 2020Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Insulin modulates vasomotor tone through vasodilator and vasoconstrictor signaling pathways. The purpose of the present work was to determine whether insulin-stimulated vasoconstriction is a pathophysiological phenomenon that can result from a combination of persistent insulin signaling, suppressed phosphatidylinositol-3 kinase (PI3K) activation, and an ensuing relative increase in MAPK/endothelin-1 (ET-1) activity. First, we examined previously published work from our group where we assessed changes in lower-limb blood flow in response to an oral glucose tolerance test (endogenous insulin stimulation) in lean and obese subjects. The new analyses showed that the peak rise in vascular resistance during the postprandial state was greater in obese compared with lean subjects. We next extended on these findings by demonstrating that insulin-induced vasoconstriction in isolated resistance arteries from obese subjects was attenuated with ET-1 receptor antagonism, thus implicating ET-1 signaling in this constriction response. Last, we examined in isolated resistance arteries from pigs the dual roles of persistent insulin signaling and blunted PI3K activation in modulating vasomotor responses to insulin. We found that prolonged insulin stimulation did not alter vasomotor responses to insulin when insulin-signaling pathways remained unrestricted. However, prolonged insulinization along with pharmacological suppression of PI3K activity resulted in insulin-induced vasoconstriction, rather than vasodilation. Notably, such aberrant vascular response was rescued with either MAPK inhibition or ET-1 receptor antagonism. In summary, we demonstrate that insulin-induced vasoconstriction is a pathophysiological phenomenon that can be recapitulated when sustained insulin signaling is coupled with depressed PI3K activation and the concomitant relative increase in MAPK/ET-1 activity.
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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 Socratic graph.