High Sucrose Diets Promote Intestinal Epithelial Cell Proliferation and Tumorigenesis in APC^Min Mice by Increasing Insulin and IGF-I Levels

Abstract

Epidemiological studies report that high sucrose consumption is associated with increased risk of colon cancer. One hypothesis is that this association is mediated by elevated circulatory insulin and IGF levels promoting intestinal proliferation. To test this hypothesis, APC ^Min mice and their wild type littermates were fed, starting at 4 wk of age, sucrose or cornstarch as the sole carbohydrate source in the absence or presence of low levels of dietary sulindac for 10 or 16 wk, respectively. APC ^Min mice fed sucrose had an increased tumor number in the proximal third of the small intestine in both studies and a higher incidence of papillary colon tumors in the 16-wk feeding study ( P ≤ 0.05). Mice fed sucrose (relative to cornstarch) had higher body weights and greater Ki67-labeling indexes in colonic epithelium than mice fed cornstarch in both feeding studies ( P ≤ 0.05). Furthermore, mice fed sucrose had higher serum glucose and liver IGF-I mRNA concentrations ( P ≤ 0.05) and tended to have higher serum insulin levels ( P = 0.08). These results support the hypothesis that high dietary sucrose intake promotes intestinal proliferation and tumorigenesis by increasing circulating levels of insulin and IGF-I.

ACKNOWLEDGMENTS

The authors thank the International Life Science Institute, North America for financial support of this research via an Alex Malaspina Future Leader Award to L. D. Bourquin. Appreciation is extended to Crystal Ybarra for assistance with animal care and tissue collection. Bing Wang is currently affiliated with the Beckman Research Institute at the City of Hope National Medical Center, Los Angeles, CA 91010. Gerd Bobe is currently a fellow in the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. John J. LaPres and Leslie D. Bourquin also are affiliated with the National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824.

Notes

^a Not all columns sum to 1,000 g/kg due to rounding.

^b Composition of AIN 93-MX mineral mix and AIN 93-VX vitamin as described in Reeves et al. (23).

^a Abbreviation is as follows: TUNEL, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling.

^b Means within a study not sharing a common subscript are different (P < 0.05).