ArticleProceedings of the National Academy of Sciences of the United States of America2021
Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- pH and Glucose Dual-Responsive Hybrid Polymeric Smart Insulin Carrier for Diabetes Treatment.Polymers · 2026Article
- Engineering a Glucose-Responsive Glucagon Prodrug Through Arginine-Phenylboronic Acid Pendant Modification.Small science · 2026Article
- On-demand insulin manufacturing using cell-free systems with an "on-column" conversion approach.New biotechnology · 2025Article
- Smart closed-loop drug delivery systems.Nature reviews bioengineering · 2025Article
- Ultrastable Insulin-Glucagon Fusion Protein Exploits an Endogenous Hepatic Switch to Mitigate Hypoglycemic Risk.ACS pharmacology & translational science · 2025Article
- A Computational Glucoregulatory Model of Liver and Glucagon for the Evaluation of Therapeutics.ACS pharmacology & translational science · 2025Article
- Evolution of the Artificial Pancreas: Components and Integration-CGMs, Insulin, and AP Systems.Journal of diabetes science and technology · 2025Review
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Article
- Article
- NIH Fifth Artificial Pancreas Workshop 2023: Meeting Report: The Fifth Artificial Pancreas Workshop: Enabling Fully Automation, Access, and Adoption.Journal of diabetes science and technology · 2024Article
- In Silico Investigation of the Clinical Translatability of Competitive Clearance Glucose-Responsive Insulins.ACS pharmacology & translational science · 2023Article
- Rational Design and Efficacy of Glucose-Responsive Insulin Therapeutics and Insulin Delivery Systems by Computation Using Connected Human and Rodent Models.Advanced healthcare materials · 2023Article
- Single-chain insulin analogs threaded by the insulin receptor αCT domain.Biophysical journal · 2022Article
- Diabetes Technology Meeting 2021.Journal of diabetes science and technology · 2022Article
- New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals.The Journal of clinical endocrinology and metabolism · 2022Review
- Synthesis and Characterization of Phenylboronic Acid-Modified Insulin With Glucose-Dependent Solubility.Frontiers in chemistry · 2022Article
- Structural principles of insulin formulation and analog design: A century of innovation.Molecular metabolism · 2021Review
- Using a synthetic switch to regulate insulin receptor activation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin-signaling requires conformational change: whereas the free hormone and its receptor each adopt autoinhibited conformations, their binding leads to structural reorganization. To test the functional coupling between insulin's "hinge opening" and receptor activation, we inserted an artificial ligand-dependent switch into the insulin molecule. Ligand-binding disrupts an internal tether designed to stabilize the hormone's native closed and inactive conformation, thereby enabling productive receptor engagement. This scheme exploited a diol sensor (
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.