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. Copyright 2009 John Wiley & Sons, Ltd.
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 humaninsulin. 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. Copyright 2009 John Wiley & Sons, Ltd.
Authors: Mark R Sommerfeld; Günter Müller; Georg Tschank; Gerhard Seipke; Paul Habermann; Roland Kurrle; Norbert Tennagels Journal: PLoS One Date: 2010-03-04 Impact factor: 3.240
Authors: Humberto Parada; Rebecca J Cleveland; Kari E North; June Stevens; Susan L Teitelbaum; Alfred I Neugut; Regina M Santella; Maria E Martinez; Marilie D Gammon Journal: Mol Carcinog Date: 2018-12-11 Impact factor: 4.784
Authors: L G Hemkens; U Grouven; R Bender; C Günster; S Gutschmidt; G W Selke; P T Sawicki Journal: Diabetologia Date: 2009-06-30 Impact factor: 10.122