Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in mutant mice lacking gastrin gene expression

Stephanie L. Cowey, Michael Quast, Ligia Maria Belalcazar, Jingwa Wei, Xiaoling Deng, Randall Given, Pomila Singh

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)2643-2653
Number of pages11
JournalCancer
Volume103
Issue number12
DOIs
StatePublished - Jun 15 2005

Keywords

  • Aberrant
  • Azoxymethane
  • Colon carcinogenesis
  • Crypt foci
  • Gastrin
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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