ArticleDiabetes2015
Transthyretin Antisense Oligonucleotides Lower Circulating RBP4 Levels and Improve Insulin Sensitivity in Obese Mice.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Concurrent Aerobic and Resistance Training Has Anti-Inflammatory Effects and Increases Both Plasma and Leukocyte Levels of IGF-1 in Late Middle-Aged Type 2 Diabetic Patients.Oxidative medicine and cellular longevity · 2017Trial
- Key Hepatokines Linking MASLD and Type 2 Diabetes: From Pathophysiological Mechanisms to Therapeutic Modulation.International journal of molecular sciences · 2026Review
- Gc inhibition preserves insulin sensitivity and reduces body weight without loss of muscle mass.JCI insight · 2025Article
- Proteomic analysis of plasma total exosomes and placenta-derived exosomes in patients with gestational diabetes mellitus in the first and second trimesters.BMC pregnancy and childbirth · 2024Article
- Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic β-cell function.Endocrine · 2024Review
- Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets.Heliyon · 2023Review
- RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Vitamin A homeostasis and cardiometabolic disease in humans: lost in translation?Journal of molecular endocrinology · 2022Review
- Plasma Transthyretin Levels and Risk of Type 2 Diabetes Mellitus and Impaired Glucose Regulation in a Chinese Population.Nutrients · 2022Article
- Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation.Metabolites · 2022Review
- Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases.International journal of molecular sciences · 2021Review
- Exploring the Physiological Role of Transthyretin in Glucose Metabolism in the Liver.International journal of molecular sciences · 2021Article
- RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia.Frontiers in endocrinology · 2021Article
- Growth hormone receptor disrupts glucose homeostasis via promoting and stabilizing retinol binding protein 4.Theranostics · 2021Article
- Association between transthyretin concentrations and gestational diabetes mellitus in Chinese women.Archives of gynecology and obstetrics · 2020Article
- RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Article
- Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders.Pharmacology & therapeutics · 2019Review
- The Stomach as an Endocrine Organ: Expression of Key Modulatory Genes and Their Contribution to Obesity and Non-alcoholic Fatty Liver Disease (NAFLD).Current gastroenterology reports · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Circulating transthyretin (TTR) is a critical determinant of plasma retinol-binding protein 4 (RBP4) levels. Elevated RBP4 levels cause insulin resistance, and the lowering of RBP4 levels improves glucose homeostasis. Since lowering TTR levels increases renal clearance of RBP4, we determined whether decreasing TTR levels with antisense oligonucleotides (ASOs) improves glucose metabolism and insulin sensitivity in obesity. TTR-ASO treatment of mice with genetic or diet-induced obesity resulted in an 80-95% decrease in circulating levels of TTR and RBP4. Treatment with TTR-ASOs, but not control ASOs, decreased insulin levels by 30-60% and improved insulin sensitivity in ob/ob mice and high-fat diet-fed mice as early as after 2 weeks of treatment. The reduced insulin levels were sustained for up to 9 weeks of treatment and were associated with reduced adipose tissue inflammation. Body weight was not changed. TTR-ASO treatment decreased LDL cholesterol in high-fat diet-fed mice. The glucose infusion rate during a hyperinsulinemic-euglycemic clamp was increased by 50% in high-fat diet-fed mice treated with TTR-ASOs, demonstrating improved insulin sensitivity. This was also demonstrated by 20% greater inhibition of hepatic glucose production, a 45-60% increase of glucose uptake into skeletal and cardiac muscle, and a twofold increase in insulin signaling in muscle. These data show that decreasing circulating TTR levels or altering TTR-RBP4 binding could be a potential therapeutic approach for the treatment of type 2 diabetes.
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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.