Insulin promotion of colon tumors in rats.
McKeown-Eyssen and Giovannucci have proposed a mechanism for colon carcinogenesis based on the similarity of the risk factors for colorectal cancer and non-insulin-dependent diabetes. They note that diets high in fat and energy and low in complex carbohydrates and a sedentary lifestyle lead to insulin resistance and hyperinsulinemia and propose that the hyperinsulinemia promotes colon carcinogenesis. In this study, we directly tested for a promoting effect of insulin on colon carcinogenesis in F344 rats. After azoxymethane initiation and injections of insulin given 5 times/week for 17 weeks, the fraction of rats with colon tumors was greater in rats receiving insulin than in rats receiving saline (79 versus 50%, respectively; P < 0.05 for tumors with maximum diameters > or = 2 mm), and the average number of tumors/ rat was also greater (2.00 versus 0.73; P < 0.001). There was no effect on body weight. Our results demonstrate that insulin in a colon tumor promoter in this rat model and support the proposed mechanism linking lifestyle factors and colon carcinogenesis.
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Department of Nutritional Sciences, University of Toronto, Ontario, Canada.
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Bruce
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D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage / Q000009:adverse effects; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D001786:Blood Glucose; D002273:Carcinogens; D007004:Hypoglycemic Agents; D007328:Insulin; D001397:Azoxymethane