Insulin-Like Growth Factor-I and Insulin Are Associated With the Presence and Advancement of Adenomatous Polyps

Abstract

Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.

Insulin Therapy and Colorectal Adenoma Risk Among Patients with Type 2 Diabetes Mellitus: A Case-Control Study in Korea

“…16,18 The IGF system is a potent growth regulator closely linked with carcinogenesis. 19 Although not consistently, several prospective, observational studies have shown an association between elevated IGF-1 levels and risk of not only CRC risk but also advanced adenoma, 7,8,18,[20][21][22] supporting the notion that IGF-1 plays a role in the biologic pathway of colorectal neoplasia, beginning at the adenoma stage. From this respect, our result may provide a strong support for the hypothesis that hyperinsulinemia may play a critical role in early stage of colorectal carcinogenesis.…”

“…Moreover, Schoen et al 7 reported that levels of insulin and IGF-1 were associated with colorectal adenomas and even more so with advanced adenomas and insulin and IGF-1 might contribute to the development and advancement of adenomatous polyps. In our study, only 37 cases of advanced adenomas were included in the adenoma group.…”

“…[4][5][6] It has been postulated that insulin resistance and resultant hyperinsulinemia is the common pathway for these environmental risk factors to promote the development of CRC. 5,7,8 In addition, Type 2 diabetes mellitus, a condition associated with hyperinsulinemia, is associated with increased risk of colorectal adenoma and cancer. [9][10][11][12] Patients with Type 2 diabetes begin to require insulin therapy when there is significant decline in endogenous insulin production; however, hyperinsulinemia is actually augmented during this phase by exogenous insulin because of the inefficiency of exogenous insulin by the progression of insulin resistance.…”

Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers

“…However, some papers have recently reported several effects of IGF-IR blockade on IR. Both a chimeric single-chain antibody against IGF-IR (scFv-Fc) and a murine antibody for IGF-IR (EM164) resulted in decreased levels of IR in vitro and in vivo despite their lack of reactivity against IR [28]. The down-regulation of IR by these anti-IGF-IR mAbs requires the co-expression of IGF-IR and is likely due to the endocytosis of hybrid IR/IGF-IR.…”

“…IGF-IR and IR can form hybrid receptors that bind IGFs at physiologic concentrations. IR and IGF-IR/IR hybrid receptors may also be involved in cancer biology as both insulin and IGF-I contribute to the development and progression of adenomatous polyps [28].…”