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Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in mutant mice lacking gastrin gene expression
Article first published online: 29 APR 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 12, pages 2643–2653, 15 June 2005
How to Cite
Cowey, S. L., Quast, M., Belalcazar, L. M., Wei, J., Deng, X., Given, R. and Singh, P. (2005), Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in mutant mice lacking gastrin gene expression. Cancer, 103: 2643–2653. doi: 10.1002/cncr.21094
- Issue published online: 2 JUN 2005
- Article first published online: 29 APR 2005
- Manuscript Accepted: 2 FEB 2005
- Manuscript Revised: 11 JAN 2005
- Manuscript Received: 18 NOV 2004
- National Institutes of Health. Grant Number: R01-CA97959
- colon carcinogenesis;
- insulin resistance;
- crypt foci;
The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates. In the current report, the authors discuss the predisposition of GAS-KO mice to develop obesity and metabolic hormonal changes that may contribute to their increased risk of colon carcinogenesis.
The weight and deposition of fat was monitored in the mice over a 14 month period, using magnetic resonance imaging and nuclear magnetic resonance techniques. Changes in plasma concentrations of ghrelin, leptin, insulin, and glucose were assessed using radioimmunoassay analysis and enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of obese versus lean GAS-KO mice and were compared with the markers in WT mice.
Increases in visceral adiposity were evident by age 2 months in GAS-KO mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1 month and preceded alterations in nonfasting leptin and ghrelin levels. The number of ACFs per mouse colon were increased significantly in the following order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin levels were 0.88 ± 0.1 ng/mL, 1.45 ± 0.3, and 2.76 ± 0.9 ng/mL in the WT, GAS-KO lean, and GAS-KO obese mice, respectively.
The current results suggest the novel possibility that loss of amidated gastrins may increase adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The increase in colon carcinogenesis may be due in part to hyperinsulinemia, increased obesity, and other associated hormone changes that were measured in GAS-KO mice. Cancer 2005. © 2005 American Cancer Society.