Zinc-Dependent Low Thymic Hormone Level in Type I Diabetes

Abstract

Zinc is required for optimal functioning of the immune system. It was recently reported that one of the best-known thymic hormones responsible for the maturation and differentiation of the thymus-derived T-lymphocyte line, i.e., serum thymic factor (STF), is biologically active only when bound to zinc ions; in this form it has been called thymulin (Zn-STF). Because low serum and tissue zinc values have been reported to occur in diabetic conditions, and because defects of T-lymphocyte-dependent functions are also present in diabetic patients, even metabolically well-controlled diabetic patients, we investigated the serum level of zinc and the plasma level of both active Zn-STF and inactive STF thymic hormones in 15 young patients suffering from type I (insulin-dependent) diabetes. Serum zinc levels were significantly reduced in diabetic conditions and did not correlate with the degree of metabolic compensation measured by glycosylated hemoglobin. In diabetes, the active form of thymulin is strongly reduced, whereas the inactive form is abnormally elevated. In vitro zinc addition to diabetic plasma samples also induces zinc saturation of inactive thymic hormone molecules: the total thymic hormone measured in these experimental conditions shows values in diabetic patients comparable with those observed in healthy age-matched individuals, suggesting that low thymulin levels recorded in diabetic conditions are due not to a thymic failure in synthesizing and secreting thymic hormone but to a peripheral defect in zinc saturation of the hormone molecules. The zinc-dependent failure of thymic hormone, present even in fairly compensated diabetic conditions, might account for the apparent insulin-independent immunological abnormalities associated with type I diabetes.

Biological consequences of zinc deficiency in the pathomechanisms of selected diseases

“…In type 2 diabetes, a single nucleotide polymorphism in SLC30A8, rs13266634 (Arg325Trp), has been reported. The ZnT8 transporter is located on dense core vesicles (DCVs) in β cells and loads the zinc cation into these secretory compartments where it then binds with and stabilizes the hexameric form of insulin [89]. It appears that functional ZnT8 facilitates autocrine and paracrine roles for the zinc ion bursts produced by β cells upon glucose stimulation [86].…”

“…After secretion, the hexameric structure of insulin dissociates into the active monomer and zinc ions, which is most likely caused by a combination of a rapid decrease in Zn 2+ pressure. Moreover, an in vitro study suggested that the Zn ions co-secreted with insulin during hyperglycemia might contribute to β cell death via a paracrine mechanism [89]. It has been hypothesized that such activity could link hyperinsulinism with β cell necrosis and the ensuing type 2 diabetes.…”

“…It has been hypothesized that such activity could link hyperinsulinism with β cell necrosis and the ensuing type 2 diabetes. The indispensable role of zinc in the insulin structure makes it a requirement when insulin analogs are prepared to ensure its activity and stabilization [89]. It is well known that decreased levels of this metal are observed in diabetes mellitus.…”

Haematological and biochemical reference values of Gambian infants

“…Deficiency of trace elements is commonly seen in malnourished infants and this is closely associated with thymic hypofunction which invariably contributes to low WBC (Mocchegiani et al . ; Rink & Gabriel ).…”

Zinc influences the in vitro development of peri‐implantation mouse embryos

“…The positive effect of Zn supplementation in these studies supports the concept that in some populations, suboptimal Zn nutrition is a risk factor for adverse pregnancy outcome. Furthermore, toxicant exposures as well as acute and chronic disease states can reduce the availability of maternal Zn to the embryo (Mocchegiani et al, 1989; Taubeneck et al, 1994). It is important to note that many nutritional studies related to reproduction consider nutrition only after pregnancy has been recognized.…”