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Cited by 179Growth Hormone and Insulin-like Growth FactorsMetabolism, Diabetes, and CancerFibroblast Growth Factor Research

Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells

Weinstein, Doron, Simon, Meital, Yehezkel, Einat, Laron, Zvi, Werner, Haim·2009·Diabetes/Metabolism Research and Reviews
DOI 10.1002/dmrr.912
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Abstract

BACKGROUND: Insulin analogues are widely used in the treatment of diabetes mellitus. Some insulin analogues were reported to display atypical activities in vitro that resemble those of insulin-like growth factor-I (IGF-I). The aim of this study was to investigate whether two long-acting insulin analogues [glargine (Lantus, Sanofi Aventis, Germany) and detemir (Levemir, Novo Nordisk, Denmark)] and two short-acting analogues [lispro (Humalog, Eli Lilly, Indianapolis, USA) and aspart (Novolog, Novo Nordisk, Denmark)] exhibit IGF-I-like activities on cultured cancer cells in comparison with IGF-I and regular human insulin. METHODS: HCT-116 (colorectal cancer), PC-3 (prostate cancer) and MCF-7 (breast adenocarcinoma) cell lines were treated with insulin, IGF-I or insulin analogues, and proliferation and protection from apoptosis were measured by cell counting and fluorescent-activated cell sorter (FACS) analysis, respectively. In addition, Western blots were used to identify signalling molecules activated by the analogues. RESULTS: Glargine, detemir and lispro had proliferative effects that resemble IGF-I action. Insulin, however, did not stimulate cellular proliferation. In addition, glargine and detemir displayed an IGF-I-like anti-apoptotic activity. Glargine, like insulin and IGF-I, induced phosphorylation of both ERK and AKT, suggesting that the analogue is able to stimulate both the ras-raf-mitogen-activated protein kinase (MAPK) and PI3K-AKT pathways. Furthermore, glargine induced both insulin receptor (IR) and IGF-IR phosphorylation. CONCLUSIONS: Glargine, detemir and lispro, unlike regular insulin, exhibit in vitro proliferative and anti-apoptotic activities in a number of cancer cell lines. These actions resemble some of the effects of IGF-I, a growth factor involved in cancer initiation and progression. Insulin had no increased IGF-I activity. The specific receptor/s involved in mediating analogues actions remains to be identified.

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Crossref · 10.1002/dmrr.912

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  • IGF-I has more potent mitogenic and anti-apoptotic activities than insulin.

    “IGF-I has more potent mitogenic and anti-apoptotic activities than insulin (58) and could act as a growth stimulus in preneoplastic and neoplastic cells that express insulin, IGF-I, and hybrid receptors (49).”

    From Diabetes and Cancer (2010) · cites this paper as [58]

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Authors
Weinstein, D., Simon, M., Yehezkel, E., Laron, Z., & Werner, H.
Affiliations
  • Tel Aviv University (IL)
  • Schneider Children's Medical Center (IL)
Corresponding author
Werner, Haim
ORCID
Venue
Diabetes/Metabolism Research and Reviews
Publisher
Wiley
Published
2009-01
Volume
25
Issue
1
Pages
41-49
ISSN
  • 1520-7552 (ISSN-L)
  • 1520-7560
DOI
10.1002/dmrr.912
OpenAlex
W2112447641
Cited by
179
References
31
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 11 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 15 · 2012: 17
FWCI
18.15
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 13 d)
Locations
  • Diabetes/Metabolism Research and Reviews (publishedVersion)
  • PubMed (publishedVersion)
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
insulin analogues, insulin-like growth factor I, glargine, detemir, insulin lispro, mitogenic activity, anti-apoptotic effects, tumor cell proliferation, ERK1/2 phosphorylation, Akt phosphorylation, MAPK signaling, PI3K/Akt signaling, insulin receptor, IGF-1 receptor, colorectal cancer, prostate cancer, breast cancer
MeSH terms
Insulin Glargine, Insulin Detemir, Adenocarcinoma, Breast Neoplasms, Cell Division, Dose-Response Relationship, Drug, Female, Humans, Insulin, Insulin-Like Growth Factor I, Male, Prostatic Neoplasms, Tumor Cells, Cultured, Colorectal Neoplasms, Apoptosis, Cell Line, Tumor, Insulin, Long-Acting, Insulin Lispro

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