ArticleDiabetes2012
A fully human, allosteric monoclonal antibody that activates the insulin receptor and improves glycemic control.
Article in Diabetes, 2012. 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, 77 citations in OpenAlex.
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- Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance.Nature communications · 2025Article
- Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET.Cell reports. Medicine · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- A stepwise activation model for the insulin receptor.Experimental & molecular medicine · 2023Review
- Insulin signaling and its application.Frontiers in endocrinology · 2023Review
- Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.Nature communications · 2022Article
- An Insulin Receptor-Binding Multifunctional Protein fromFoods (Basel, Switzerland) · 2022Article
- The Insulin Receptor: An Important Target for the Development of Novel Medicines and Pesticides.International journal of molecular sciences · 2022Review
- Agonist antibody discovery: Experimental, computational, and rational engineering approaches.Drug discovery today · 2022Review
- Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity.Biomolecules · 2021Review
- Camel Milk Targeting Insulin Receptor-Toward Understanding the Antidiabetic Effects of Camel Milk.Frontiers in nutrition · 2021Review
- Anti-Insulin Receptor Antibodies Improve Hyperglycemia in a Mouse Model of Human Insulin Receptoropathy.Diabetes · 2020Article
- Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy.Endocrine reviews · 2019Review
- Perspective: The promises of a holistic view of proteins-impact on antibody engineering and drug discovery.Bioscience reports · 2019Article
- Evaluation of anti-insulin receptor antibodies as potential novel therapies for human insulin receptoropathy using cell culture models.Diabetologia · 2018Article
- Unique pharmacology of a novel allosteric agonist/sensitizer insulin receptor monoclonal antibody.Molecular metabolism · 2018Article
Corrections and comments
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Authors and funding
23 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many patients with diabetes mellitus (both type 1 and type 2) require therapy to maintain normal fasting glucose levels. To develop a novel treatment for these individuals, we used phage display technology to target the insulin receptor (INSR) complexed with insulin and identified a high affinity, allosteric, human monoclonal antibody, XMetA, which mimicked the glucoregulatory, but not the mitogenic, actions of insulin. Biophysical studies with cultured cells expressing human INSR demonstrated that XMetA acted allosterically and did not compete with insulin for binding to its receptor. XMetA was found to function as a specific partial agonist of INSR, eliciting tyrosine phosphorylation of INSR but not the IGF-IR. Although this antibody activated metabolic signaling, leading to enhanced glucose uptake, it neither activated Erk nor induced proliferation of cancer cells. In an insulin resistant, insulinopenic model of diabetes, XMetA markedly reduced elevated fasting blood glucose and normalized glucose tolerance. After 6 weeks, significant improvements in HbA(1c), dyslipidemia, and other manifestations of diabetes were observed. It is noteworthy that hypoglycemia and weight gain were not observed during these studies. These studies indicate, therefore, that allosteric monoclonal antibodies have the potential to be novel, ultra-long acting, agents for the regulation of hyperglycemia in 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.