ArticleMolecular metabolism2017
Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose homeostasis in mouse models of diabetes.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Emerging Breakthroughs in Nano-Ginseng Innovations and Their Therapeutic Implications in Type 2 Diabetes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research.Biomolecules · 2025Review
- Exploring cutting-edge approaches in diabetes care: from nanotechnology to personalized therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Research progress on the application of nanoparticles delivery in the treatment of atherosclerosis: implications for therapeutic interventions.Frontiers in cell and developmental biology · 2025Review
- Nanomedicine in the Treatment of Diabetes.International journal of molecular sciences · 2024Review
- Small interfering RNA (siRNA) as a potential gene silencing strategy for diabetes and associated complications: challenges and future perspectives.Journal of diabetes and metabolic disorders · 2024Review
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- Enhanced Effects of Intermittent Fasting by Magnetic Fields in Severe Diabetes.Research (Washington, D.C.) · 2024Article
- Cellular Alterations in Carbohydrate and Lipid Metabolism Due to Interactions with Nanomaterials.Journal of functional biomaterials · 2023Review
- The Protective Role of Apelin in the Early Stages of Diabetic Retinopathy.International journal of molecular sciences · 2022Article
- Recent advances in the application of nanomedicine for the treatment of diabetes.Nanomedicine (London, England) · 2022Article
- Targeting the Gut Mucosal Immune System Using Nanomaterials.Pharmaceutics · 2021Review
- DUSP6 protects murine podocytes from high glucose‑induced inflammation and apoptosis.Molecular medicine reports · 2020Article
- Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.EMBO reports · 2020Article
- Hepatic Glucagon Signaling Regulates PCSK9 and Low-Density Lipoprotein Cholesterol.Circulation research · 2019Article
- Nanoparticles That Deliver RNA to Bone Marrow Identified by in Vivo Directed Evolution.Journal of the American Chemical Society · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHyperglucagonemia is present in many forms of diabetes and contributes to hyperglycemia, and glucagon suppression can ameliorate diabetes in mice. Leptin, a glucagon suppressor, can also reverse diabetes in rodents. Lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) effectively targets the liver and is in clinical trials for the treatment of various diseases. We compared the effectiveness of glucagon receptor (Gcgr)-siRNA delivered via LNPs to leptin in two mouse models of diabetes.
methodsGcgr siRNA encapsulated into LNPs or leptin was administered to mice with diabetes due to injection of the β-cell toxin streptozotocin (STZ) alone or combined with high fat diet (HFD/STZ).
resultsIn STZ-diabetic mice, a single injection of Gcgr siRNA lowered blood glucose levels for 3 weeks, improved glucose tolerance, and normalized plasma ketones levels, while leptin therapy normalized blood glucose levels, oral glucose tolerance, and plasma ketones, and suppressed lipid metabolism. In contrast, in HFD/STZ-diabetic mice, Gcgr siRNA lowered blood glucose levels for 2 months, improved oral glucose tolerance, and reduced HbA1c, while leptin had no beneficial effects.
conclusionsWhile leptin may be more effective than Gcgr siRNA at normalizing both glucose and lipid metabolism in STZ diabetes, Gcgr siRNA is more effective at reducing blood glucose levels in HFD/STZ 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.