Insulin Injections Promote the Growth of Aberrant Crypt Foci in the Colon of Rats

Abstract

The main objective of the present study was to test the hypothesis that exogenous insulin would enhance colon carcinogenesis. Thirty-six female F344 rats, fed ad libitum a low fat rodent chow, received a single azoxymethane injection (20 mg/kg), and were randomized a week later to two groups. Control rats were given 5 days a week a s.c. saline injection, and experimental rats were given ultralente bovine insulin, 20 U/kg. The promoting effect of insulin injections was assessed by the multiplicity (number of crypts) of aberrant crypt foci after 100 d of treatment (72 injections). The rats given insulin ate more and were heavier than controls (215 ± 11 vs. 182 ± 7 g, p<0.001). Insulin injections also increased the amount of abdominal fat, the plasma triglycerides, and the insulinemia, and decreased blood glucose (all p<0.05). The number of aberrant crypt foci was the same in both groups, but their multiplicity was significantly increased by the insulin injections (2.8 ± 0.3 vs. 2.5 ± 0.2 crypt/focus in controls, p=0.007). Besides, the proportion of sialomucin producing foci was higher in insulin injected rats than in controls (p=0.04). These data show that exogenous insulin can promote colon carcinogenesis in rats, and suggest that lifestyle and diets leading to low blood insulin might protect humans against colorectal cancer.