Zinc and diabetes

Abstract

Zn 2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn 2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions. Abbreviation ISG: Insulin Secreting Granules; T2D: Type 2 Diabetes; T1D: Type 1 Diabetes; 2 Diabetes mellitus is a common metabolic disease, affecting approximately 9% of the adult population worldwide. It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].These early studies, as well as much more recent findings showing association between T2D risk and the inheritance of gene variants encoding a critical β cell Zn 2+ transporter, ZnT8[5] have generated considerable interest in the role of Zn 2+ in diabetes aetiology and as a possible therapeutic target [6]. Zinc and the diabetic patientScott and Fisher were the first to report a direct link between zinc and diabetes in patients.While assessing the insulin content in the pancreas of diabetic patients compared to nondiabetic cadavers, they showed that in the former group zinc content was reduced by 75 % [7].Epidemiological studies also demonstrated that diabetes and whole body zinc status are associated [8][9][10][11]. In T1D and T2D patients, serum zinc levels are significantly decreased [9][10][11], this being associated with an increased zinc urinary loss [8].Zinc may have important anti-oxidant properties, as it acts as a cofactor of the superoxide dismutase enzyme which regulates the detoxification of reactive oxygen species, regulating the expression and protecting against the oxidative stress induced by chronic hyperglycaemia (for review, [12]). Furthermore, zinc inhibits alpha-ketoglutarate-dependent mitochondrial respiration suggesting that Zn 2+ can interfere with mitochondrial antioxidant production and may also stimulate production of reactive oxygen [13].Zinc supplementation h...

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

“…Any chemistry that oxidizes or modifies these sulfhydryls lowers the zinc buffering capacity and increases the availability of free zinc ions. Free zinc ion concentrations are higher in cells from diabetic cardiac cells/tissues (61), decrease under hypoxia in β-cells (62), and double when β-cells are exposed to higher glucose concentrations (63). When free zinc ion concentrations increase zinc can bind to macromolecules/proteins that otherwise would not interact with zinc and affect their functions.…”

Association of Serum Zn/Cu Ratio With Handgrip Strength and Hospitalization in Japanese Patients With Type 2 Diabetes

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Zinc (Zn) is negatively associated with the incidence of coronary heart diseases in patients with type 2 diabetes [1], and copper (Cu) may also play a pivotal role in the pathogenesis of diabetes [2]. We reported that the serum Zn/Cu ratio was positively associated with glycemic control in patients with type 2 diabetes [3].

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Цукровий Діабет: Роль Генетичних Факторів У Розвитку Захворюванн

“…Огляд літератури /Literature Review/ может модифицировать экспрессию SLC30A8 и способствовать развитию СД 2-го типа [95].…”