ArticlePloS one2012
Molecular characterisation of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- A framework for the in vitro evaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues.Carcinogenesis · 2015Pooled it
- Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence.Breast cancer research : BCR · 2015Pooled it
- Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing.BMJ open diabetes research & care · 2021Trial
- A rare homozygousBMJ open diabetes research & care · 2024Article
- Article
- Minimizing Mitogenic Potency of Insulin Analogues Through Modification of a Disulfide Bond.Frontiers in endocrinology · 2022Article
- Structural principles of insulin formulation and analog design: A century of innovation.Molecular metabolism · 2021Review
- The Influence of Anti-Diabetic Drugs on Prostate Cancer.Cancers · 2021Review
- Increased insulin receptor binding and increased IGF-1 receptor binding are linked with increased growth of L6hIR cell xenografts in vivo.Scientific reports · 2020Article
- Insulin-Independent Reversal of Type-1 Diabetes Following Transplantation of Adult Brown Adipose Tissue Supplemented With IGF-1.Transplantation direct · 2019Article
- The Role of Insulin Glargine and Human Insulin in the Regulation of Thyroid Proliferation Through Mitogenic Signaling.Frontiers in endocrinology · 2019Article
- Article
- Insulin glargine affects the expression ofIranian journal of basic medical sciences · 2018Article
- A Novel Strategy to Prevent Advanced Atherosclerosis and Lower Blood Glucose in a Mouse Model of Metabolic Syndrome.Diabetes · 2018Article
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Article
- Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes.Diabetologia · 2016Article
- Effect of the long-acting insulin analogues glargine and degludec on cardiomyocyte cell signalling and function.Cardiovascular diabetology · 2016Article
- Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant.American journal of physiology. Endocrinology and metabolism · 2015Article
- Ligand-Binding Affinity at the Insulin Receptor Isoform-A and Subsequent IR-A Tyrosine Phosphorylation Kinetics are Important Determinants of Mitogenic Biological Outcomes.Frontiers in endocrinology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThere is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10.
methodsWe measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types.
resultsDetemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤ 1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs.
conclusionsDetailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir.
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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 Socratic graph.