Why diabetes patients are more prone to the development of colon cancer?

Type II diabetes mellitus (T2D) develops as the consequence of relative insulin insufficiency. The onset of T2D is characterized by insulin resistance, and in most cases, with hyperinsulinemia for compensation. Extensive basic and clinical examinations have identified a large profile of T2D susceptibility genes and multiple risk factors, including obesity and sedentary life style, which are shared by colon cancer development. The intestinal endocrine L cells produce an incretin hormone, namely glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion in blood glucose dependent manner, pancreatic beta cell proliferation and neogenesis. It has been shown that in T2D patients, postprandial GLP-1 secretion level is reduced. I hypothesize that during the development of insulin resistance, intestinal endocrine L cells produce more GLP-1 for compensation. This compensatory response involves the activation of Wnt signaling pathway and the cross-talk between Wnt and insulin signaling pathways. A pathological consequence of this compensation will be the stimulated expression of proto-oncogenes, including c-Myc. (C) 2008 Elsevier Ltd. All rights reserved.