Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Ppublish 34 citations
PubMed: 33787922 DOI: 10.1093/jmcb/mjab024
Diabetes pathogenesis and management: the endothelium comes of age.
J Mol Cell Biol 13(7):500-512
Authors: Kaitlin M Love, Eugene J Barrett, Steven K Malin, Jane E B Reusch, Judith G Regensteiner, Zhenqi Liu
Affiliations
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, USA.
- Division of Endocrinology, Metabolism and Nutrition, Rutgers University, New Brunswick, NJ, USA.
- New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA.
- Institute of Translational Medicine and Research, Rutgers University, New Brunswick, NJ, USA.
- Center for Women's Health Research, University of Colorado School of Medicine, Aurora, CO, USA.
- Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, USA.
Abstract
Endothelium, acting as a barrier, protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered function. Endothelial insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease, can co-exist with and even contribute to the development of metabolic insulin resistance, and promote vascular complications in those affected. The impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location, resulting in decreased arterial plasticity, increased atherosclerosis and vascular resistance, and decreased tissue perfusion. Women with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease, likely related to differential sex-hormone endothelium effects. Thus, reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications, in the resistance arteries lead to better blood pressure control, and in the microvasculature lead to less microvascular complications and more effective tissue perfusion. Multiple diabetes therapeutic modalities, including medications and exercise training, improve endothelial insulin action and vascular function. This action may delay the onset of type 2 diabetes and/or its complications, making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.
MeSH
Diabetes Mellitus, Exercise, Insulin Resistance, Insulin, Blood, Molecular Biology, Arteries, Therapeutics, Tissues, Endothelium, Diabetes Mellitus, Type 2
Cited by
- Obesity: causes, consequences, treatments, and challenges. J Mol Cell Biol, 2022
- Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade. Front Immunol, 2022
- Joint association of triglyceride glucose index (TyG) and body roundness index (BRI) with stroke incidence: a national cohort study. Cardiovasc Diabetol, 2025
- Interplay of fatty acids, insulin and exercise in vascular health. Lipids Health Dis, 2025
- Impact of Free Fatty Acids on Vascular Insulin Responses Across the Arterial Tree: A Randomized Crossover Study. J Clin Endocrinol Metab, 2024
- Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes. J Clin Endocrinol Metab, 2025
- Microvascular Skeletal-Muscle Crosstalk in Health and Disease. Int J Mol Sci, 2023
- Gender differences in the health workforce in China: an analysis of national data. J Mol Cell Biol, 2025
- Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy. Front Endocrinol (Lausanne), 2023
- Pathways of Coagulopathy and Inflammatory Response in SARS-CoV-2 Infection among Type 2 Diabetic Patients. Int J Mol Sci, 2023
- New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors. Front Pharmacol, 2022
- Extracellular Vesicles in Metabolic and Vascular Insulin Resistance. J Vasc Res, 2024
- From MASLD to PAD: Looking for Cardiovascular Disease Starting from Metabolic Status. Medicina (Kaunas), 2024
- Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes. Am J Physiol Heart Circ Physiol, 2024
- Metformin prevents endothelial oxidative stress and microvascular insulin resistance during obesity development in male rats. Am J Physiol Endocrinol Metab, 2022
- Intermediate versus morning chronotype has lower vascular insulin sensitivity in adults with obesity. Diabetes Obes Metab, 2024
- Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function. Theranostics, 2022
- Hyperglycemia-induced DNA damage response activates DNA-PK complex to promote endothelial ferroptosis in type 2 diabetic cardiomyopathy. Theranostics, 2025
- Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From Liquid Biopsy to New Omics Technologies and Noninvasive Circulating Biomarkers. Int J Mol Sci, 2022