Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I
Abstract
The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. The breast cancer cell lines MCF-7 and SKBR-3, and the osteosarcoma cell line SaOS-2 were used. Gene expression was determined by real-time RT-PCR and receptor protein quantified by ELISAs. Receptor phosphorylation was assessed by immunoprecipitation and Western blot. Mitogenic effect was determined as (3)H-thymidine incorporation into DNA. The gene expression of insulin receptor (IR) varied between 4.3-7.5 x 10(-3) and the expression of IGF-IR between 7.7-147.7 x 10(-3) in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. The IGF-IR was phosphorylated by IGF-I at a concentration of 10(-10)-10(-9) M. All three polypeptides stimulated DNA synthesis in MCF-7, SKBR-3, and SaOS-2 cells. SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. In SKBR-3 and SaOS-2 cells, glargine tended to be more potent than human insulin to stimulate DNA synthesis. Our results suggest that glargine, compared to human insulin, has little or no increased mitogenic effect in malignant cells expressing IGF-IRs.
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Substantial prior research has emphasized differences between human insulin and analog insulins with respect to binding affinity to the IGF-I receptor, including evidence that insulin glargine has much higher affinity and higher mitogenic potency than human insulin or other analogs.
“Substantial prior research has emphasized differences between human insulin and analog insulins with respect to binding affinity to the IGF-I receptor, including evidence that insulin glargine has much higher affinity, and higher mitogenic potency, than human insulin or other analogs (120–122).”
From Diabetes and Cancer (2010) · cites this paper as [122]
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“[48] tested insulin glargine on MCF-7 and SKBR-3 cells and found a slightly increased mitogenic activity of insulin glargine without statistical significance.”
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“Consistent with data reported in the literature (Liefvendahl and Arnqvist, 2008), AspB10 insulin was more potent than human insulin with an EC50 0.”
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“Furthermore, one study did include a positive control (IGF1) [24], but this compound did not show a positive effect, which questions the sensitivity of their experiments.”
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“No significant differences were found between glargine and human insulin on DNA synthesis, although glargine was slightly more potent than insulin (Liefvendahl and Arnqvist, 2008).”
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Diabetes and pancreatic cancer.
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“Similar outcome was reported in breast cancer cell line MCF-7 cells that had the highest expression of IGT-I receptor [39].”
ResultMayer, D., & Chantelau, E. A. (2010) · Archives of Physiology and Biochemistry · doi:10.3109/13813451003631439 · Cited by 34 · see citing works
“Lantus was shown to exert increased mitogenicity compared to regular insulin on MCF-7 breast cancer cells in vitro (Liefvendahl & Arnqvist, 2008; Mayer et al., 2008; Shukla et al., 2009a; Weinstein et al., 2009); this effect was found with low concentrations of glargine (Liefvendahl & Arnqvist,…”
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Azar, M., & Lyons, T. J. (2009) · F1000 Medicine Reports · doi:10.3410/m2-4 · Cited by 31 · see citing works
“In addition, according to some authors [10,11], glargine compared with human insulin does not seem to display increased mitogenic effects, despite its higher affinity for the IGF-1 receptor [10]; rather, any type of insulin has the potential to promote growth in cancer cells, especially if administered at”
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“…at subnanomolar insulin concentrations, and associated with high fold responses L6-hIR and the parental L6 cells were synchronized in G0/G1 under optimal conditions as described in “Materials and methods” for flask 3 and exposed to tenfold dilution series of human insulin, IGF-1, and X-10 (Fig.”
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“An increased mitogenic potency has also been observed in prostate and bowel [82], but not in thyroid [83], pancreas [84], or bladder [85] cancer cells; discordant results have been reported in osteosarcoma cell lines [80, 86].”
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“In contrary, it was reported that insulin glargine, which would be ultimately required by many diabetic patients [140], has elevated mitogenic potency [89,141,142], supporting the aforementioned clinical findings as well as the importance of this metabolic pathway in oncology.”
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“Hence, hyperinsulinemia, exogenous insulin or insulin analogs [9-13] most probably favors cancer in patients with diabetes.”
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Investigating the Role of Insulin and Its Analogs in Breast Cancer Proliferation
Garg, N., Kamal, C. M., & Chander, H. (2026) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-026-10821-7
- Authors
- Liefvendahl, E., & Arnqvist, H.
- Affiliations
- Linköping University (SE)
- Venue
- Hormone and Metabolic Research
- Publisher
- Georg Thieme Verlag KG
- Published
- 2008-06
- Volume
- 40
- Issue
- 6
- Pages
- 369-374
- ISSN
- 0018-5043 (ISSN-L)
- 1439-4286
- OpenAlex
- W2066464682
- Cited by
- 53
- References
- 0
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 6
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone and Metabolic Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Barndiabetesfonden
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Keywords
- glargine, insulin analogues, IGF-1 receptor, insulin receptor, mitogen response, insulin-like growth factor I, des(1-3)IGF-I, breast cancer cells, osteosarcoma cells, receptor phosphorylation, DNA synthesis, cell proliferation
- MeSH terms
- Insulin Glargine, Analysis of Variance, Breast Neoplasms, Cell Division, Humans, Hypoglycemic Agents, Insulin, Insulin-Like Growth Factor I, Mitogens, Osteosarcoma, Tumor Cells, Cultured, Receptor, IGF Type 1, Statistics, Nonparametric, Insulin, Long-Acting
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