Abstract
Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, works as cofactor in numerous enzymatic reactions and it behaves as antioxidant molecule. PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is now becoming clearer. Inadequate intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes. Growing evidence shows that diabetes and cancer are correlated not only because they share same risk factors but also because diabetic patients have a higher risk of developing tumors, although the underlying mechanisms remain elusive. In this review, we will explore data obtained in Drosophila revealing the existence of a connection between vitamin B6, DNA damage and diabetes, as flies in the past decade turned out to be a promising model also for metabolic diseases including diabetes. We will focus on recent studies that revealed a specific role for PLP in maintaining chromosome integrity and glucose homeostasis, and we will show that these aspects are correlated. In addition, we will discuss recent data identifying PLP as a putative linking factor between diabetes and cancer.
Highlights
Edited by: Maria Grazia Giansanti, Istituto di Biologia e Patologia Molecolari (IBPM), Consiglio Nazionale Delle Ricerche (CNR), Italy
Pyridoxal -phosphate (PLP) works as antioxidant molecule by quenching oxygen reactive species (ROS) (Ehrenshaft et al, 1999) and counteracting the formation of Advanced Glycation End products (AGEs), genotoxic compounds associated with senescence and diabetes (Booth et al, 1997)
In this review we focus on the role of PLP in diabetes and cancer we present evidence from flies suggesting that suggesting more specialist readings for the other pathologies incorrect PLP intake could represent a cancer risk factor for (Hellmann and Mooney, 2010; di Salvo et al, 2012)
Summary
PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is becoming clearer. Inadequate intake of this vitamin increases the risk of many cancers; PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes. It has been proposed that PLP may impact on insulin resistance by controlling the expression of genes involved in adipogenesis (Moreno-Navarrete et al, 2016) Another hypothesis is that PLP deficiency might cause insulin resistance through an increase of homocysteine due to impairment of enzymes such as cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CGL), which require PLP as a coenzyme (Liu et al, 2016).
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