Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis

Aims/hypothesis Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potentia...

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Bibliographic Details
Published in:Diabetologia 2010-05, Vol.53 (5), p.966-970
Main Authors: Rensing, K. L, Houttuijn Bloemendaal, F. M, Weijers, E. M, Richel, D. J, Büller, H. R, Koolwijk, P, van der Loos, C. M, Twickler, Th. B, von der Thüsen, J. H
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
Angiogenesis
Antibodies
Biological and medical sciences
Breast Neoplasms - metabolism
Cancer
Cells, Cultured
Colonic Neoplasms - metabolism
Diabetes
Diabetes. Impaired glucose tolerance
Disease Progression
Drug dosages
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Endothelium, Vascular - metabolism
Epithelial Cells - metabolism
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Growth factors
Human Physiology
Humans
Immunohistochemistry
Insulin
Insulin - analogs & derivatives
Insulin - metabolism
Insulin-Like Growth Factor I - metabolism
Internal Medicine
Kidney Neoplasms - metabolism
Laboratories
Lung Neoplasms - metabolism
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Neovascularization, Pathologic - metabolism
Pancreas
Pancreatic Neoplasms - metabolism
Receptor, Insulin - metabolism
Short Communication
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Summary:Aims/hypothesis Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic cells and by its IGF-1 related properties. However, insulin-stimulated angiogenesis could be an additional factor involved in tumour progression and clinical outcomes associated with cancer. Methods Five types of human adenocarcinoma (breast, colon, pancreas, lung and kidney) were evaluated for the presence of insulin receptors (IRs) on angiogenic structures. In an in vitro angiogenesis assay, various commercially available insulin compounds were evaluated for their potential to increase capillary-like tube formation of human microvascular endothelial cells (hMVEC). Insulin compounds used were: human insulin, insulin lispro (B28Lys,B29Pro human insulin), insulin glargine and insulin detemir (B29Lys[e-tetradecanoyl],desB30 human insulin). Results Insulin receptors were found to be strongly expressed on the endothelium of microvessels in all evaluated adenocarcinomas, in addition to variable expression on tumour cells. Low or no detectable expression of IRs was seen on microvessels in extratumoral stroma. Incubation with commercially available insulin compounds increased capillary-like tube formation of hMVEC in vitro. Conclusions/interpretation Our results suggest that all tested insulin compounds may stimulate tumour growth by enhancing local angiogenesis. Future studies need to confirm the association between insulin therapy in type 2 diabetes and tumour progression.
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-010-1687-y