Glucose Metabolism Disorders and the Risk of Cancer

Abstract

Diabetes and cancer are diseases which take the size of an epidemic spread across the globe. Those diseases are influenced by many factors, both genetic and environmental. Precise knowledge of the complex relationships and interactions between these two conditions is of great importance for their prevention and treatment. Many epidemiological studies have shown that certain types of cancer, especially gastrointestinal cancers (pancreas, liver, colon) and also the urinary and reproductive system cancers in women are more common in patients with diabetes or related metabolic disorders. There are also studies showing the inverse relationship between diabetes and cancer, or the lack of it, but they are less numerous and relate mainly to prostate cancer or squamous cell carcinoma of the esophagus. Epidemiological studies, however, do not say anything about the mechanisms of these dependencies. For this purpose, molecular research is needed on the metabolism of cells (including tumor cells) and on metabolic dysfunctions that arise due to changes in the cell environment taking place in the sick, as well as in the intensely treated human organism.

Inflammation, Aging and Cancer: Friend or Foe?

“…For example, steroids or insulin play important roles not only in the function of reproductive organs and regulation of fluid homeostasis and/or metabolic pathways and immune responses to stress, but they are also involved in physiology, function and remodeling of bone, neuronal function, myelination and neurogeneration of brain and CNS and/or membrane-associated fatty acid metabolism (Bosch et al, 2002, Brunello et al, 2011, Campisi 2011, Chung et al, 2011, Goronzy and Wavand 2005, Hotamisisligil 2006, Khatami 1990, Li et al, 1986, Mikkola and Clarkson 2002, Sansoni et al, 2008, Simon and Balkau 2010, van Kruijsdijk et al, 2009). Insulin deficiency, insulin-resistance or hyper-insulinimia, or glucose toxicity and hyperglycemia of diabetes-induced increased glycosylation of proteins (advanced glycation end-products-AGE and their receptors RAGE) are associated with disturbances in transport and metabolism of important nutrients (e.g., ascorbic acid, pyridoxal phosphate, myo-inositol, etc), increased oxidative stress, accumulation of ROS, and co-expression of pro-and anti-inflammatory mediators such as NF-kB, VEGF, TNF-, IL1a, IL-6, IL-8, IL-12, and Ikappa B kinase (IKK-), platelets' CD40L, VCAM-1, in endothelial, hepatocytes or myeloid cells and/or tissues that are insulin-dependent (e.g., muscle, liver, adipocytes) or insulin-independent (e.g., vasculature, kidney, nerves, retina, RPE, lens) for glucose transport or metabolism , 1990, Li et al, 1986, Park et al, 2005, Pisan 2008, Piatkiewicz and Czech 2011, Simon and Balkau 2010, Stern et al, 2002. The relationship between diabetes, inflammation and production of AGE/RAGE and the increased risk of certain cancers has been the topic of many recent studies (Piatkiewicz and Czech 2011, Simon and Balkau 2010, Simon et al, 2010, Zhang and Hu 2010.…”

“…Insulin deficiency, insulin-resistance or hyper-insulinimia, or glucose toxicity and hyperglycemia of diabetes-induced increased glycosylation of proteins (advanced glycation end-products-AGE and their receptors RAGE) are associated with disturbances in transport and metabolism of important nutrients (e.g., ascorbic acid, pyridoxal phosphate, myo-inositol, etc), increased oxidative stress, accumulation of ROS, and co-expression of pro-and anti-inflammatory mediators such as NF-kB, VEGF, TNF-, IL1a, IL-6, IL-8, IL-12, and Ikappa B kinase (IKK-), platelets' CD40L, VCAM-1, in endothelial, hepatocytes or myeloid cells and/or tissues that are insulin-dependent (e.g., muscle, liver, adipocytes) or insulin-independent (e.g., vasculature, kidney, nerves, retina, RPE, lens) for glucose transport or metabolism , 1990, Li et al, 1986, Park et al, 2005, Pisan 2008, Piatkiewicz and Czech 2011, Simon and Balkau 2010, Stern et al, 2002. The relationship between diabetes, inflammation and production of AGE/RAGE and the increased risk of certain cancers has been the topic of many recent studies (Piatkiewicz and Czech 2011, Simon and Balkau 2010, Simon et al, 2010, Zhang and Hu 2010. It should also be noted that chronic inflammation in patients with neurodegenerative diseases, asthma or diabetes are reported to increase the risks for certain site-specific cancers (e.g., lung cancer in asthmatic patients, or liver and pancreas in diabetics) and decreased risk for certain other cancers (e.g., prostate in diabetics) (Brunello and Kappor 2011b, Piatkkiewicz and Czech 2011, Stern et al, 2002, Vena et al, 1985, Vesterinen et al, 1993, Vingeri et al 2009, Zhang and Hu 2010.…”

Molecular basis of carcinogenesis in diabetic patients (Review)

“…Diabetic patients have dysfunctional innate and adaptive immune systems, resulting in increased susceptibility to infections and subsequent development of immune system disorders (1,63,64). immune system dysfunction may ultimately lead to increased risk of cancer development.…”

“…Prior studies demonstrated increased nK cellular activity in physically active individuals, especially athletes (1,(65)(66)(67). reduced activity was observed in individuals with high-fat diets.…”

“…into cells, as well as regulation of intracellular signaling pathways, insulin significantly affects both the cellular transcriptome and proteome (1). Moreover, high serum insulin concentration inhibits autophagocytosis, proteasome activity, and apoptosis (2).…”