ArticlePloS one2012
Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.
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 33 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 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
- Trial
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Association of high insulin receptor expression with poor prognosis in patients with breast cancer.Gland surgery · 2023Article
- Article
- Dysmetabolism and Neurodegeneration: Trick or Treat?Nutrients · 2022Review
- Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells.Scientific reports · 2022Article
- The brain as an insulin-sensitive metabolic organ.Molecular metabolism · 2021Review
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition.Molecular therapy. Nucleic acids · 2018Article
- Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment.CNS neuroscience & therapeutics · 2018Review
- The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors.BMC cancer · 2018Article
- Identification of insulin-sensitizing molecules acting by disrupting the interaction between the Insulin Receptor and Grb14.Scientific reports · 2017Article
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Tau deletion promotes brain insulin resistance.The Journal of experimental medicine · 2017Article
- Prevention of tumour cell apoptosis associated with sustained protein kinase B phosphorylation is more sensitive to regulation by insulin signalling than stimulation of proliferation and extracellular signal-regulated kinase.Molecular and cellular biochemistry · 2017Article
- Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.PLoS pathogens · 2017Article
- CRISPR Cas9-guided chromatin immunoprecipitation identifies miR483 as an epigenetic modulator of IGF2 imprinting in tumors.Oncotarget · 2017Article
- Obesity and Cancer Mechanisms: Cancer Metabolism.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R), present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET) assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3)) production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3) production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells.
resultsAmong the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3) production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3) production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin.
conclusionGlargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in MCF-7 cells.
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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.