Mariano Bizzarri*, Simona Dinicola* and Alessandra Cucina Pages 5200 - 5210 ( 11 )
Insulin resistance indicates a deregulated set of biochemical pathways and physiological functions involved in the pathogenesis of a number of diseases, including type 2 diabetes and cancer. Conversely, a number of synthetic and natural insulin sensitizers, including inositol, have been recognized to exert both anti-diabetic as well as anti-cancer properties. Inositol participates in insulin transduction signaling, and deregulated inositol metabolism has been ascertained in several conditions associated with insulin resistance. Two distinct inositolphosphoglycans released upon insulin stimulation act as insulin-mimetic by counteracting hyperinsulinemia, hyperglycemia and their metabolic complications. Additionally, inositol may directly interfere with both glucose metabolism and carcinogenesis by modulating a number of critical processes downstream of insulin stimulation, including anti-oxidant defenses, oxidative glucose metabolism and endocrine modulation. A selected cluster of biochemical factors (PI3K/Akt, PDH and AMPK-related pathways), that are presently considered putative targets for anticancer treatments, are also specifically modulated by inositol or its derivatives. What is more, studies on inositol mechanism of action paved the way in understanding that both insulin resistance and cancer share a few perturbed, critical biochemical pathways. Asides from the basic investigations, preliminary studies in vivo demonstrated the beneficial effect of inositol in fostering glucose homeostasis as well as in antagonizing cancer growth. Thereby, inositol fulfills the requirement to target both insulin resistance and cancer, and its clinical usefulness deserves to be adequately addressed by specific, randomized trials.
myo-inositol, PI3K/Akt, inositol-glycan, insulin resistance, aerobic glycolysis, anti-cancer.
Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Department of Surgery “Pietro Valdoni”, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Department of Surgery “Pietro Valdoni”, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome