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Insulin X10 Revisited: a Super-mitogenic Insulin Analogue

Overview
Journal Diabetologia
Specialty Endocrinology
Date 2011 Jun 3
PMID 21633908
Citations 28
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Abstract

The molecular safety of insulin analogues has received a great deal of attention over the last year. In particular, attention has been directed to the mitogenic properties of insulin analogues as compared with human insulin. Understanding the mechanisms implicated in mediating mitogenic effects of insulin is therefore of particular interest. In this review we detail the story of the rapid-acting insulin analogue known as X10, which was the first insulin analogue in clinical development, but ended up being discontinued at an early clinical development stage following findings of mammary tumours in female Sprague-Dawley rats. The molecular characteristics of insulin X10, along with its interaction at both the IGF-1 receptor and the insulin receptor, have provided us with important insights into mechanisms implicated in metabolic and mitogenic signalling of insulin analogues.

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References
1.
Glendorf T, Knudsen L, Stidsen C, Hansen B, Hegelund A, Sorensen A . Systematic evaluation of the metabolic to mitogenic potency ratio for B10-substituted insulin analogues. PLoS One. 2012; 7(2):e29198. PMC: 3285154. DOI: 10.1371/journal.pone.0029198. View

2.
Tran T, Medline A, Bruce W . Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev. 1996; 5(12):1013-5. View

3.
Schwartz G, Burke G, KATSOYANNIS P . A superactive insulin: [B10-aspartic acid]insulin(human). Proc Natl Acad Sci U S A. 1987; 84(18):6408-11. PMC: 299085. DOI: 10.1073/pnas.84.18.6408. View

4.
Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A . Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002; 277(42):39684-95. DOI: 10.1074/jbc.M202766200. View

5.
Renehan A, Tyson M, Egger M, Heller R, Zwahlen M . Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008; 371(9612):569-78. DOI: 10.1016/S0140-6736(08)60269-X. View