ArticleThe Journal of clinical investigation1999
Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03883412 (Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes), which is not on this map. Cited by 215 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)
Who cites it
215 citing papers in PubMed, 601 citations in OpenAlex.
- Early microvascular recruitment modulates subsequent insulin-mediated skeletal muscle glucose metabolism during lipid infusion.Diabetes care · 2013 · on this mapTrial
- Hyperinsulinemia fails to augment ET-1 action in the skeletal muscle vascular bed in vivo in humans.American journal of physiology. Endocrinology and metabolism · 2008Trial
- Insulin mimetics and non-canonical insulin receptor signaling: mechanisms and disease relevance.Experimental & molecular medicine · 2026Review
- Molecular and Cellular Underpinnings of Primary Hypertension: An Integrative Mechanistic Framework.Journal of cellular physiology · 2026Review
- Fatty liver regeneration after partial hepatectomy: an experimental study based on intravoxel incoherent motion and T2Magma (New York, N.Y.) · 2026Article
- Feeding the invaders: how metabolic imbalance shapes infection and biofilm development.FEMS microbiology reviews · 2026Review
- The Association of Insulin Sensitivity, Secretion, and Clearance With Subclinical Atherosclerosis in Middle-Aged Adults Without Diabetes: A Cross-Sectional Analysis of the SCAPIS Cohort.Journal of diabetes · 2025Article
- Repurposing Antidiabetic Drugs for Cerebrovascular Diseases: Causal Evidence from Drug Target Mendelian Randomization and Colocalization.Molecular neurobiology · 2025Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Association between triglyceride-glucose index in early pregnancy and risk of preeclampsia: a multicenter retrospective cohort study.Lipids in health and disease · 2025Article
- Review
- Interplay of fatty acids, insulin and exercise in vascular health.Lipids in health and disease · 2025Review
- EndothelialCurrent diabetes reviews · 2025Review
- Comprehensive treatment of diabetic endothelial dysfunction based on pathophysiological mechanism.Frontiers in medicine · 2025Review
- Association between estimated glucose disposal rate and incident cardiovascular disease in a population with Cardiovascular-Kidney-Metabolic syndrome stages 0-3: insights from CHARLS.Frontiers in cardiovascular medicine · 2025Article
- Insulin resistance, CaFrontiers in physiology · 2025Review
- Insulin receptors in vascular smooth muscle cells regulate plaque stability of atherosclerosis.Cardiovascular research · 2024Article
- Article
- The Complex Immunological Alterations in Patients with Type 2 Diabetes Mellitus on Hemodialysis.Journal of clinical medicine · 2024Review
- Interleukin-6 as a Director of Immunological Events and Tissue Regenerative Capacity in Hemodialyzed Diabetes Patients.Medical sciences (Basel, Switzerland) · 2024Article
155 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Both insulin resistance and hyperinsulinemia have been reported to be independent risk factors for cardiovascular diseases. However, little is known regarding insulin signaling in the vascular tissues in insulin-resistant states. In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. In euglycemic clamp studies, insulin infusion greatly increased tyrosine phosphorylation of IRbeta- and IRS-2-associated PI 3-kinase activity in the aorta of lean rats, but only slight increases were observed in obese rats. In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.