Hyperinsulinemia, But Not Other Factors Associated with Insulin Resistance, Acutely Enhances Colorectal Epithelial Proliferation in Vivo
- 1 April 2006
- journal article
- Published by The Endocrine Society in Endocrinology
- Vol. 147 (4), 1830-1837
- https://doi.org/10.1210/en.2005-1012
Abstract
The similarity in risk factors for insulin resistance and colorectal cancer (CRC) led to the hypothesis that markers of insulin resistance, such as elevated circulating levels of insulin, glucose, fatty acids, and triglycerides, are energy sources and growth factors in the development of CRC. The objective was thus to examine the individual and combined effects of these circulating factors on colorectal epithelial proliferation in vivo. Rats were fasted overnight, randomized to six groups, infused iv with insulin, glucose, and/or Intralipid for 10 h, and assessed for 5-bromo-2-deoxyuridine labeling of replicating DNA in colorectal epithelial cells. Intravenous infusion of insulin, during a 10-h euglycemic clamp, increased colorectal epithelial proliferation in a dose-dependent manner. The addition of hyperglycemia to hyperinsulinemia did not further increase proliferation. Intralipid infusion alone did not affect proliferation; however, the combination of insulin, glucose, and Intralipid infusion resulted in greater hyperinsulinemia than the infusion of insulin alone and further increased proliferation. Insulin infusion during a 10-h euglycemic clamp decreased total IGF-I levels and did not affect insulin sensitivity. These results provide evidence for an acute role of insulin, at levels observed in insulin resistance, in the proliferation of colorectal epithelial cells in vivo.Keywords
This publication has 42 references indexed in Scilit:
- A Prospective Study of C-Peptide, Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-1, and the Risk of Colorectal Cancer in WomenCancer Epidemiology, Biomarkers & Prevention, 2005
- Insulin and IGF-1 stimulate the β-catenin pathway through two signalling cascades involving GSK-3β inhibition and Ras activationOncogene, 2001
- A specific function for phosphatidylinositol 3-kinase α (p85α-p110α) in cell survival and for phosphatidylinositol 3-kinase β (p85α-p110β) in de novo DNA synthesis of human colon carcinoma cellsOncogene, 2000
- No evidence of tumor growth stimulation in human tumors in vitro following treatment with recombinant human growth hormoneAnti-Cancer Drugs, 2000
- Effect of Insulin on FarnesyltransferaseJournal of Biological Chemistry, 1998
- Altered regulation of insulin-like growth factor binding protein-I in patients with polycystic ovary syndromeJournal of the Society for Gynecologic Investigation, 1995
- Insulin and Insulin‐like Growth Factor 1 Stimulate Proliferation of Metastatic Variants of Colon Carcinoma 26Japanese Journal of Cancer Research, 1989
- Immunohistochemical identification of proliferating cells in organ culture using bromodeoxyuridine and a monoclonal antibody.Journal of Histochemistry & Cytochemistry, 1986
- Insulin binding by normal and neoplastic colon tissueInternational Journal of Cancer, 1985
- Stimulation of deoxythymidine incorporation in the colon of rats treated intrarectally with bile acids and fatsCarcinogenesis: Integrative Cancer Research, 1983