ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2017
Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
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- The impact of metformin on myocardial hypertrophy: an updated systematic review, meta-analysis, and meta-regression of randomized controlled trials.Diabetology & metabolic syndrome · 2025Review
- Triglyceride-glucose index association with kidney function in adults; a population-based study.BMC endocrine disorders · 2025Article
- Pilot study on photoacoustic imaging and confocal Raman spectroscopy-derived biomarkers for assessing structural and physiological skin changes in atopic dermatitis and metabolic diseases.Biomedical optics express · 2025Article
- T2D-LVDD: neural network-based predictive models for left ventricular diastolic dysfunction in type 2 diabetes.Diabetology & metabolic syndrome · 2025Article
- The correlation between HOMA-IR and cardiometabolic risk index among different metabolic adults: a cross-sectional study.Acta diabetologica · 2025Article
- Synergistic Amelioration of Letrozole-induced Polycystic Ovary Syndrome in Rats: A Therapeutic Approach with Apple Cider Vinegar and Metformin Combination.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling.Molecular aspects of medicine · 2024Review
- Pyroptosis in Diabetic Peripheral Neuropathy and its Therapeutic Regulation.Journal of inflammation research · 2024Review
- The association of dietary insulinemic indices with PI3K, PTEN, and Akt gene expressions in visceral and subcutaneous adipose tissues among individuals undergoing abdominal surgery.Frontiers in nutrition · 2024Article
- Diet-induced glial insulin resistance impairs the clearance of neuronal debris in Drosophila brain.PLoS biology · 2023Article
- Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.Clinical science (London, England : 1979) · 2023Review
- Lymphatic Clearance and Pump Function.Cold Spring Harbor perspectives in medicine · 2023Review
- Alpha-ketoglutarate partially alleviates effects of high-fat high-fructose diet in mouse muscle.EXCLI journal · 2023Article
- Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- A Synopsis of the Associations of Oxidative Stress, ROS, and Antioxidants with Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2022Review
- DNA methylation and expression profiles of placenta and umbilical cord blood reveal the characteristics of gestational diabetes mellitus patients and offspring.Clinical epigenetics · 2022Article
- Ribosomal biogenesis regulator DIMT1 controls β-cell protein synthesis, mitochondrial function, and insulin secretion.The Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.
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Registered trials
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