**2. Zinc in T2D pathogenesis**

Zinc (Zn) is a necessary micronutrient which has an essential role in insulin metabolism [14, 15]. In pancreatic beta cells, Zn is required for the synthesis, storage and insulin secretion [79]. It has been described in diabetic subjects pancreas is zinc deficiency compared to normal subject. These data confirmed that zinc is involved in insulin signaling pathways [16]. Zn may stimulate energy consumption in skeletal muscle and brown adipose tissue and may increase the pancreatic insulin content and improve the glucose tolerance test [17]. Zn is found largely in cereals, animal protein and seafood [18]. Zn absorption can be inhibited by iron. Zn is transported across cell membranes via ZnT family's transporters [19].

In diabetes diseases (insulin resistance, metabolic syndrome), Zn is considered important mainly because: (i) it plays a major role in the stabilization of insulin hexamers and the hormone pancreatic storage [20] and (ii) it is an efficient antioxidant [21]. Zinc deficiency in type 2 diabetes is mainly due to a significant urinary zinc loss [22], nevertheless, this Zinc deficiency is not very significant versus healthy subject [23]. Lower Zn plasma concentrations were found in T2D to relate of cardiovascular risk metabolic syndrome factors [24], and reduced Zn levels in diabetics appear to be related to increased risk for coronary artery disease [25]. It has been described that zinc effects mimic the insulin action mainly via the glycogen synthesis/degradation enzymes signaling pathways [26]. Other mechanisms include Cu/Zn-superoxide dismutase regulation via the post receptor proteins Akt and PI3-kinase via NF\_B [27]. On the other hand, some particular forms of Zn have been discovered in ob/ ob mice, such Zn-α 2-glycoprotein is an adipokine which stimulates energy expenditure in skeletal muscle and brown adipose tissue, resulting in reductions in glycaemia, triglycerides and Free Fatty Acids. Their level is lower in obese human subcutaneous and visceral adipose tissue and liver, but interestingly does not appear to be related to insulin resistance [28].
