ArticleDiabetes2014
Proinsulin-transferrin fusion protein as a novel long-acting insulin analog for the inhibition of hepatic glucose production.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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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
13 citing papers in PubMed, 26 citations in OpenAlex.
- Current Situation on Diabetes Management: New Weapons Fighting the Disease in 2025.Current drug targets · 2026Review
- Molecular engineering approaches to half-life extension of therapeutic biomolecules.Frontiers in pharmacology · 2026Review
- Research Advances in Fusion Protein-Based Drugs for Diabetes Treatment.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Seed- and leaf-based expression of FGF21-transferrin fusion proteins for oral delivery and treatment of non-alcoholic steatohepatitis.Frontiers in plant science · 2022Article
- Enhanced insulin receptor interaction by a bifunctional insulin-transferrin fusion protein: an approach to overcome insulin resistance.Scientific reports · 2020Article
- Insulin Fused to Apolipoprotein A-I Reduces Body Weight and Steatosis in DB/DB Mice.Frontiers in pharmacology · 2020Article
- Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus.Molecular metabolism · 2019Article
- Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec.International journal of molecular sciences · 2018Article
- Insulin analogues in type 1 diabetes mellitus: getting better all the time.Nature reviews. Endocrinology · 2017Review
- Pursuit of a perfect insulin.Nature reviews. Drug discovery · 2016Review
- Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2015Review
- Tissue barriers and novel approaches to achieve hepatoselectivity of subcutaneously-injected insulin therapeutics.Tissue barriersReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Proinsulin-transferrin (ProINS-Tf) fusion protein was evaluated for its in vivo pharmacokinetics, efficacy, and mechanism. Our previous studies have shown that ProINS-Tf was converted to active insulin-transferrin (INS-Tf) via the transferrin (Tf)-receptor-mediated pathway in hepatoma cells. We hypothesized that this fusion protein can be administered as a prodrug and be converted to a biologically active protein with specificity for the liver versus other insulin (INS)-sensitive tissues (muscle and adipose). Administration as an inactive prodrug with liver-specific action compared with other INS-sensitive tissues conceivably reduces negative side effects seen with other INS analogs. In this report, the data show that ProINS-Tf exhibited a slow, but sustained, in vivo hypoglycemic efficacy and long plasma half-life. The fusion protein showed activity in the liver, as evidenced by decreased expression of two key hepatic glucose production (HGP) enzymes, PEPCK and glucose-6-phosphatase, and increased glycogen levels under feeding conditions. Furthermore, the INS receptor (IR) phosphorylation (activation) in liver and muscle tissues was compared with postinjection of INS or ProINS-Tf. While INS activated IR in both the liver and muscle, ProINS-Tf only showed activation in the liver. Thus, ProINS-Tf fusion protein can potentially be administered as a prodrug with sustained Tf-mediated activation and selectivity in inhibiting HGP.
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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.