Zinc and insulin metabolism

Abstract

A review of experimental studies of the effect of zinc nutrition on insulin metabolism is presented. In addition to a short introduction to the synthesis, secretion, and action of insulin, the effects of zinc deficiency-specifically on glucose tolerance, insulin secretion, insulin synthesis and storage, and on total insulin-like activity-are dealt with. The concentrations of zinc and chromium in serum, pancreas, and liver are compared to those of zinc-deficient animals and pair-fed controls.In contrast to pair-fed controls, zinc-deficient rats had unaltered proinsulin contents after glucose stimulation, but they showed a diminished glucose tolerance, lowered serum insulin content, and an elevated total insulin-like activity. The serum zinc concentration of the deficient animals was greatly reduced and did not change during glucose stimulation, whereas it rose in the case of the pair-fed controls. The serum chromium concentration increased in both groups in response to glucose stimulation. In the pancreas of the deficient animals, the zinc concentration was reduced 60% and it increased during the glucose tolerance test. In the liver there were no significant differences. The chromium concentrations were elevated in both the pancreas and liver of the zinc-deficient rats by 60 and 100%, respectively, and were not influenced by glucose injection.These studies show clearly that nutritional zinc deficiency influences insulin metabolism and action.

Metal ions affect insulin-degrading enzyme activity

“…We carried out enzymatic digestions of B20-30, in the presence or absence of copper(II), aluminum(III) and zinc(II), metals chosen for their important role in neurodegenerative diseases [24,26,66,67]. Moreover, since copper enters the cell as copper(I) through high-affinity plasma membrane copper transporters or low affinity permeases [68] and IDE is mainly cytosolic [1], it is interesting to analyze the effect of both oxidation states on B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) processing. Furthermore, as silver belongs to the same group of copper and silver(I) has the same chemistry of copper(I), we have also performed studies using this ion, in order to have a replication of the copper(I) results without any possible invalidation due to copper(I) oxidation problems (although we worked in a reducing environment, copper(I) could be oxidized to copper(II) during the incubation with the enzyme).…”

“…To assess how metal ions affect the IDE enzymatic activity, steady state kinetics on the B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) peptide in the presence and in the absence of the above mentioned ions were performed. Fig.…”

“…6. Lineweaver-Burk plot of the enzymatic processing by IDE of (○) B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in the absence of metals; (x) B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in the presence of 100 μM copper(II); (*) B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in the presence of 100 μM zinc(II). Increasing concentrations of substrate were incubated with 10 nM IDE in 0.5 mM phosphate buffer at pH 7.3.…”

“…In the presence of 100 μM silver(I) IDE enzymatic activity toward the B(20-30) peptide is abolished and data are not reported. Table 2 Catalytic parameters for the enzymatic processing of the peptide B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) by IDE and the effect of the addition of 100 μM copper(II) or of 100 μM zinc(II) at pH 7.3 and 37°C. by a hydroxide bound to the zinc(II) ion [71] that can be stabilized by the T27 of the B20-30.…”

“…Recently, zinc [27] and copper [28] have been identified to have a crucial role on insulin action and, ultimately, in diseases such as DM2. In particular, zinc deficiency seems to facilitate diabetes mellitus and its cardiovascular complications [29,30]. Although some studies have demonstrated antidiabetogenic properties of zinc supplementation in both animal models and humans, the efficacy is still controversial and the observation that all patients could benefit from ion administration is too simplistic [31][32][33][34].…”