ArticleJCI insight2016
One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Calcium dysregulation in diabetic cardiomyopathy & heart failure with preserved ejection fraction.Frontiers in cardiovascular medicine · 2026Review
- The metabolic role of corticotropin-releasing hormone receptor 2 and its UCN peptides: emerging therapeutic potential.Skeletal muscle · 2025Review
- Human skin CD141iScience · 2023Article
- Effects ofHuman gene therapy · 2023Article
- Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity.Nature communications · 2023Article
- Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1.FEBS open bio · 2023Article
- Organ-Specific Glucose Uptake: Does Sex Matter?Cells · 2022Article
- Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss.Obesity (Silver Spring, Md.) · 2022Review
- Article
- Review
- Urocortin 2 Gene Transfer Improves Heart Function in Aged Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice.Human gene therapy · 2019Article
- Significant alteration of liver metabolites by AAV8.Urocortin 2 gene transfer in mice with insulin resistance.PloS one · 2019Article
- Sexually dimorphic metabolic responses mediated by CRFBiology of sex differences · 2018Article
- Effects of Urocortin 2 Versus Urocortin 3 Gene Transfer on Left Ventricular Function and Glucose Disposal.JACC. Basic to translational science · 2018Article
- Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers.Molecular biology of the cell · 2017Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Using mice rendered insulin resistant with high fat diets (HFD), we examined blood glucose levels and insulin resistance after i.v. delivery of an adeno-associated virus type 8 encoding murine urocortin 2 (AAV8.UCn2). A single i.v. injection of AAV8.UCn2-normalized blood glucose and glucose disposal within weeks, an effect that lasted for months. Hyperinsulinemic-euglycemic clamps showed reduced plasma insulin, increased glucose disposal rates, and increased insulin sensitivity following UCn2 gene transfer. Mice with corticotropin-releasing hormone type 2-receptor deletion that were rendered insulin resistant by HFD showed no improvement in glucose disposal after UCn2 gene transfer, indicating that the effect requires UCn2's cognate receptor. We also demonstrated increased glucose disposal after UCn2 gene transfer in db/db mice, a second model of insulin resistance. UCn2 gene transfer reduced fatty infiltration of the liver in both models of insulin resistance. UCn2 increases Glut4 translocation to the plasma membrane in skeletal myotubes in a manner quantitatively similar to insulin, indicating a mechanism through which UCn2 operates to increase insulin sensitivity. UCn2 gene transfer, in a dose-dependent manner, is insulin sensitizing and effective for months after a single injection. These findings suggest a potential long-term therapy for clinical 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.