Diabetes mellitus and cancer: a system of insulin-like growth factors

Abstract

Diabetes mellitus and malignant tumors are among the most common and complex diseases. Epidemiological studies have shown a strong relationship between these pathologies. The causality of this relationship has not yet been unambiguously established, but a number of probable biological mechanisms have been proposed to explain it through the effects of hyperglycemia, hyperinsulinemia on the process of oncogenesis. An important role in this is played by the axis of insulin-like growth factors, their receptors and binding proteins (IGF / IGFR / IGFBP). The review provides data on the structural elements of the insulin / IGF / IGFR / IGFBP signaling axis and their internal relationships in diabetes mellitus and in the development of malignant tumors. Significant changes in the axis that occur during the formation of the diabetic environment prepare the background, which, under certain conditions, can lead to the stimulation or inhibition of tumor development. The considered signaling system, playing a significant role in the physiology of normal cells, often functions as a decisive factor in the survival of tumor cells, providing fine context-dependent regulation of many cellular processes associated with oncogenesis. However, despite many years of in-depth studies of the pathogenesis of diabetes mellitus and malignant tumors, the molecular mechanisms of the relationship between these pathologies are still largely unclear, and the internal heterogeneity of pathologies complicates research and interpretation of the results, leaving many questions.

Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model

“…Cancer is widely recognized as a global common cause of mortality from noncommunicable diseases 3 . A number of studies reported that many types of cancers complicated with DM are among the most common and complex diseases, and epidemiological data support a consistent link between DM and cancer risk, development, and mortality 4,5 …”

“…3 A number of studies reported that many types of cancers complicated with DM are among the most common and complex diseases, and epidemiological data support a consistent link between DM and cancer risk, development, and mortality. 4,5 Colorectal cancer (CRC) has become the third most common cancer worldwide and is responsible for the second cause of cancer-related death, although it is a preventable disease. 6 Studies prove that the pre-existing DM is considered to be an independent risk factor that promotes CRC carcinogenesis and an exacerbation factor.…”

Long‐term survival analysis of patients with stage IIIB‐IV non‐small cell lung cancer complicated by type 2 diabetes mellitus: A retrospective propensity score matching analysis

“…Previous studies have shown that DM affects the prognosis of cancer patients, including patients with breast, colorectal, and liver cancers 5–7 . In addition, it has been shown that type 2 DM (T2DM) promotes tumor cell proliferation and metastasis vis‐à‐vis hyperglycaemia and insulin‐like growth factor‐1(IGF‐1) 8 . In addition, it has been shown that DM‐induced modification of advanced glycation end‐products hinders invasive metastasis of lung cancer cells 9 .…”

“… 5 , 6 , 7 In addition, it has been shown that type 2 DM (T2DM) promotes tumor cell proliferation and metastasis vis‐à‐vis hyperglycaemia and insulin‐like growth factor‐1(IGF‐1). 8 In addition, it has been shown that DM‐induced modification of advanced glycation end‐products hinders invasive metastasis of lung cancer cells. 9 Therefore, we reviewed the medical records of patients with NSCLC diagnosed in our hospital from January 2015 to December 2018 to analyze the clinicopathological characteristics of patients with T2DM, determine the effect of T2DM on the overall survival (OS) of patients with NSCLC, and evaluate whether T2DM affects the long‐term prognosis of patients with NSCLC.…”

Metformin in the prevention of colorectal cancer with diabetes mellitus

“…В недавнем обзоре Франциянц Е. М. с соавт., подробно обсуждаются современные взгляды на значение системы инсулиноподобных факторов роста и, в частности, указывается, что злокачественному фенотипу в значительной степени способствуют нарушения регуляции оси инсулиноподобных факторов роста (IGF -Insulin-like growth factor 1) связывающих их белков (IGFBP -nsulin-like growth factor-binding protein) -изменение биодоступности лигандов инсулиноподобных факторов роста 1,2 (IGF-1,-2), сверхэкспрессия рецепторов к инсулиноподобному фактору роста 1 (IGF1R), нарушение регуляции нижестоящих сигнальных эффекторов. Хроническая гиперинсулинемия способствует увеличению уровня биодоступного IGF-1 (за счет увеличения уровня IGF-1 и снижения уровня связывающих белков IGFBP-1, -2, -3), а также увеличению образования гибридных рецепторов инсулина и IGF1R, тем самым увеличивая митогенный потенциал клетки [42]. Таким образом, снижая гиперинсулинемию, метформин демонстрирует непрямой противоопухолевый эффект.…”