Marginal Zinc Deficiency Promotes Pancreatic Islet Enlargement While Zinc Supplementation Improves the Pancreatic Insulin Response in Zucker Diabetic Fatty Rats.

Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to ß-cell exhaustion.

Zinc Supplementation Reduces Testicular Cell Apoptosis in Mice and Improves Spermatogenic Dysfunction Caused by Marginal Zinc Deficiency.

Zinc (Zn) is an important trace element in the human body and plays an important role in growth, development, and male reproductive functions. Marginal zinc deficiency (MZD) is common in the human population and can cause spermatogenic dysfunction in males. Therefore, the aim of this study was to investigate methods to improve spermatogenic dysfunction caused by MZD and to further explore its mechanism of action. A total of 75 4-week-old male SPF ICR mice were randomly divided into five groups (control, MZD, MZD + ZnY2, MZD + ZnY4, and MZD + ZnY8, 15 mice per group). The dietary Zn content was 30 mg/kg in the control group and 10 mg/kg in the other groups. From low to high, the Zn supplementation doses administered to the three groups were 2, 4, and 8 mg/kg·bw. After 35 days, the zinc content, sperm quality, activity of spermatogenic enzymes, oxidative stress level, and apoptosis level of the testes in mice were determined. The results showed that MZD decreased the level of Zn in the serum, sperm quality, and activity of spermatogenic enzymes in mice. After Zn supplementation, the Zn level in the serum increased, sperm quality was significantly improved, and spermatogenic enzyme activity was restored. In addition, MZD reduced the content of antioxidants (copper-zinc superoxide dismutase (Cu-Zn SOD), metallothionein (MT), and glutathione (GSH) and promoted malondialdehyde (MDA) production. The apoptosis index of the testis also increased significantly in the MZD group. After Zn supplementation, the level of oxidative stress decreased, and the apoptosis index in the testis was reduced. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) showed that the expression of B-cell lymphoma-2 (Bcl-2) mRNA and Bcl-2/BCL2-associated X (Bax) in the control group decreased in testicular cells, and their expression was restored after Zn supplementation. The results of this study indicated that Zn supplementation can reduce the level of oxidative stress and increase the ability of testicular cells to resist apoptosis, thereby improving spermatogenic dysfunction caused by MZD in mice.

Marginal Zinc Deficiency Aggravated Intestinal Barrier Dysfunction and Inflammation through ETEC Virulence Factors in a Mouse Model of Diarrhea.

Zinc is both essential and inhibitory for the pathogenesis of enterotoxigenic Escherichia coli (ETEC). However, the accurate effects and underlying mechanism of marginal zinc deficiency on ETEC infection are not fully understood. Here, a marginal zinc-deficient mouse model was established by feeding mice with a marginal zinc-deficient diet, and ETEC k88 was further administrated to mice after antibiotic disruption of the normal microbiota. Marginal zinc deficiency aggravated growth impairment, diarrhea, intestinal morphology, intestinal permeability, and inflammation induced by ETEC k88 infection. In line with the above observations, marginal zinc deficiency also increased the intestinal ETEC shedding, though the concentration of ETEC in the intestinal content was not different or even decreased in the stool. Moreover, marginal zinc deficiency failed to change the host's zinc levels, as evidenced by the fact that the serum zinc levels and zinc-receptor GPR39 expression in jejunum were not significantly different in mice with ETEC challenge. Finally, marginal zinc deficiency upregulated the relative expression of virulence genes involved in heat-labile and heat-stable enterotoxins, motility, cellular adhesion, and biofilm formation in the cecum content of mice with ETEC infection. These findings demonstrated that marginal zinc deficiency likely regulates ETEC infection through the virulence factors, whereas it is not correlated with host zinc levels.

Comparison of Thymulin Activity with Other Measures of Marginal Zinc Deficiency.

Activity of the immunoregulatory peptide thymulin reflects differences in zinc status. This study compared thymulin activity with four other zinc status measures in rats fed zinc at either 5 or 25 ppm. Rats fed the lower zinc showed the following results compared with rats with adequate zinc intake: serum thymulin activity 61% lower, serum zinc 31% lower, serum extracellular superoxide dismutase 18% lower, serum 5'-nucleotidase activity 26% lower, and liver metallothionein 28% lower. Thus, thymulin activities showed more sensitivity to restricted zinc intake than did four other parameters.

Zinc Nutritional Status in Patients with Cystic Fibrosis.

BACKGROUND: Zinc is an essential nutrient for all forms of life and its deficiency affects the normal growth and development of human beings. OBJECTIVE: The main aim was to investigate zinc nutritional status by serum zinc concentration (SZC) and dietary zinc intake and their association in cystic fibrosis (CF) patients. METHODS: A cross-sectional study was conducted in CF patients. Anthropometric measurements and respiratory and pancreatic tests were conducted. Hypozincemia was determined by SZC while using atomic absorption spectrophotometry and dietary zinc deficiency by prospective 72-h dietary surveys. RESULTS: Mean SZC (87.2 ± 16.7 µg/dL) and dietary zinc intake (97 ± 26.9% Dietary Reference Intake) were normal. Three of 17 patients with CF (17.6%) had hypozincemia and four (23.5%) had a dietary zinc deficiency. No patient with dietary zinc deficiency had hypozincemia. A positive and significant association was observed between SZC and Z-score of BMI-for-age (p = 0.048) and weight-for-height (p = 0.012) and between dietary zinc intake and energy intake (EI, p = 0.036) and Z-score of weight-for-high (p = 0.029). CONCLUSION: SZC was associated with the nutritional status, expressed as BMI (Body Mass Index) and weight-for-height Z score, and dietary zinc intake with EI and weight-for-height Z-score. No patient with hypozincemia had dietary zinc deficiency. This situation should alert us to a marginal zinc deficiency and it may explain why there were no overlapping cases between the two groups. We suggest that probably 41% of the cases in this study would be at elevated risk of zinc deficiency and a zinc supplementation may be considered.