As shown in Zaafar’s report, the level of IGF-1 and VEGF were all increased in diabetic mice and diabetic mice had higher susceptibility to DMH-induced colon cancer compared to nondiabetics. In current study, the hypothesis about the possible mechanisms involved in DM-related cancer was focused on the changes of glycolytic enzymes’ activity. Recent studies have shown that several molecules involved in the Warburg effect may be rational targets for cancer therapy. All functions in cells are energy-dependent. The oxidation of glucose through mitochondrial oxidative phosphorylation can produce 30–32 molecules of net ATP per molecule of glucose, but glycolysis generates only two molecules of ATP. HK and PK are key enzymes in glycolysis. Tumor cells exhibit a high rate of glycolysis under aerobic conditions, a phenomenon known as the Warburg effect. It had been reported that insulin could induce HK gene transcription, and this, in turn, increased glucose phosphorylation in these cells. A study by Mansor showed that the activity of PDH, a highly regulated enzyme of mitochondrial glucose metabolism, was significantly decreased in the diabetic model. PDH is also negatively regulated by PDK via phosphorylation, and the level of PDK has been shown to be significantly increased in diabetic models. The phosphorylation of PDH can prevent the movement of pyruvate into the mitochondrial matrix. The results of current study showed that the activities of HK and PK significantly increased in diabetic rats, whereas the activity of PDH was reduced. In addition, the activities of PK and HK in tumoral tissues were AMN107 in vivo significant higher than that in peritumoral tissues. The imbalance of carbohydrate metabolism between glycolysis and oxidative phosphorylation could result in the generation of lactic acid and hydrogen ions. The acidic microenvironment provides a proliferative advantage for tumorigenesis. In addition, many intermediate products in glycolysis can be exploited by tumor cells to synthesize proteins, nucleic acids and lipids, thereby providing the necessary materials for the growth and proliferation of tumor cells. These data indicated that the increasing activity of glycolytic enzymes in diabetes might play a role in the occurrence of colorectal cancer. However, the detailed mechanism needs further investigation. In conclusion, our findings demonstrated that type 2 diabetes mellitus is a high risk factor for colorectal carcinogenesis. The mechanism for this risk may involve the dysregulation of glucose metabolism in diabetes. Hyperglycemia and hyperinsulinemia in diabetic mellitus might impact the activity of enzymes catalyzing the biochemical reactions of carbohydrate metabolism. The high rate of glycolysis in colon tissues provided a proliferative advantage for tumorigenesis. This study indicated several rational targets for the prevention of diabetic complications and tumor therapy. Recent evolution of the repertoire of molecules involved in the function of the immune system has resulted in substantial divergence in the composition and functions of the gene families to which these molecules belong. Even among mammals, different families of molecules may carry out equivalent functions in different species. While the functions of many molecules in immunity are well conserved between mammalian and avian species, in other cases there is extensive divergence in molecular repertoires, with cytokines and chemokines providing examples. These differences often involve gene duplication followed by functional diversification. Thus evolution has led to variety in molecular details in spite of more conserved underlying mechanisms in solutions to the problems of infection.