Zinc deficiency affects insulin secretion and alters insulin-regulated metabolic signaling in rats.

BACKGROUND: The essential trace element zinc is important in stabilizing pancreatic insulin secretion. Zinc not only influences the synthesis of insulin but also affects its activity. Insulin not only exerts a hypoglycemic effect but also regulates glucose and lipid metabolisms in insulin target organs. In this study, we aimed to determine changes to pancreatic ß cells and insulin secretion induced by different zinc concentrations and to evaluate the effect of zinc deficiency on glucose intolerance, insulin resistance, and insulin target organs via changing insulin levels. METHODS: We set up two experimental trials. In the first trial, male Sprague Dawley (SD) rats were divided into three groups. Group one (ZnC) received a standard diet, group two (ZnF) was given a zinc-free diet, and group three (ZnFC) was initially fed a zinc-free diet followed by a reversion to the standard diet. After sacrifice, we observed changes in blood parameters, including insulin, and examined alterations in pancreatic tissue using immunostaining, with focus on the localization of pancreatic ß-cells. In the second trial, male SD rats were split into two groups, with one receiving a standard diet and the other a zinc-free diet. Oral glucose tolerance and insulin tolerance tests were then performed. After sacrifice, we evaluated changes in lipid and glucose metabolism within insulin target organs using quantitative polymerase chain reaction. RESULTS: In the first trial, blood insulin levels and the area of insulin-positive staining in pancreatic ß-cells decreased in the ZnF compared to the ZnC group. The ZnFC group did not show recovery in either blood insulin levels or the area of insulin-positive staining in pancreatic ß-cells. In the second trial, no differences were observed in glucose tolerance or insulin resistance between the ZnC and ZnF groups. However, changes in the expression of insulin target genes were noted in the liver and adipose tissue in the ZnF group. CONCLUSION: We reveal that dietary zinc concentrations not only affect the concentration of insulin in the blood but also impact the localization of pancreatic ß-cells involved in insulin production. Furthermore, our results suggest that changes in blood insulin levels, induced by different zinc concentrations, could cause metabolic alterations in insulin target organs such as the liver and adipose tissue. This study sheds more light on the role of zinc in insulin-regulated metabolic diseases.

Cytomegalovirus-related sepsis-like syndrome in very premature infants in Japan.

BACKGROUND: Very premature infants are at high risk of developing a symptomatic postnatal cytomegalovirus (CMV) disease, such as CMV-related sepsis-like syndrome (CMV-SLS). To address the limited data regarding its clinical features, a nationwide survey of CMV-SLS was conducted. METHODS: A questionnaire regarding CMV status and the clinical outcomes of CMV-SLS was sent to centers with reported cases of CMV-SLS. RESULTS: Twelve CMV-SLS cases, nine confirmed and three probable cases, were reported during the 3-year survey period. The median gestational age and birthweight were 25 weeks and 547 g, respectively. At disease onset, the median age was 49 days, and the corrected age was 31 weeks. Untreated breast milk was given in four cases (33%), whereas frozen breast milk was given in nine (75%). No specific symptoms and laboratory data regarding CMV-SLS were found. CONCLUSIONS: Very premature infants developed CMV-SLS after 1 month of age. There are no symptoms and signs specific for the diagnosis of CMV-SLS, so CMV-SLS should be considered as a differential diagnosis for premature infants who have unexplained sepsis-like symptoms during the convalescent phase.

Potential role of mitochondrial damage and S9 mixture including metabolic enzymes in ZnO nanoparticles-induced oxidative stress and genotoxicity in Chinese hamster lung (CHL/IU) cells.

The present study was designed to examine genotoxicity induced by 10-40 nm zinc oxide (ZnO) nanoparticles using the in vitro system. The frequency of micronuclei was significantly increased in a dose-dependent manner when cultured Chinese hamster lung (CHL/IU) cells were exposed to ZnO nanoparticles for 24, 48 and 72 h in the continuous treatment method. The maximal frequency of micronuclei was observed in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 125 µM. The frequency of micronuclei was profoundly enhanced when CHL/IU cells were exposed to ZnO nanoparticles in the presence vs. absence of S9 mixture including metabolic enzymes in the short-term treatment method, demonstrating an increase in the formation of micronuclei by S9 mixture. The maximal frequency of micronuclei was seen in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 140 µM. Similar results were obtained in chromosome aberrations, particularly structural aberrations. Surprisingly, administration of the superoxide radical scavenger, tempol, completely abolished an increase in the frequency of micronuclei in the presence or absence of S9 mixture, indicating a central role of superoxide radical in the formation of micronuclei. Indeed, reactive oxygen species (ROS) generation was elevated by simultaneous incubation of S9 mixture and ZnO nanoparticles and by exposure of CHL/IU cells to ZnO nanoparticles in the presence or absence of S9 mixture. An electron microscopic examination revealed mitochondrial damage in CHL/IU cells exposed to ZnO nanoparticles, indicating the participation of mitochondrial dysfunction in ROS generation in this setting. These observations suggest that ZnO nanoparticles evoke genotoxicity through superoxide radical-induced oxidative stress derived from mitochondrial damage in CHL/IU cells. S9 mixture appears to contribute to a further increase in genotoxicity through the generation of superoxide radical by metabolic activation of ZnO nanoparticles.

Indium chloride-induced micronuclei in in vivo and in vitro experimental systems.

OBJECTIVES: The aim of this study was to investigate the genotoxic effects of indium trichloride (InCl(3)·4H(2)O; InCl(3)) using the in vivo bone marrow micronucleus test and the in vitro CHL/IU cell micronucleus test. METHOD: BALB/c mice were administered a single intraperitoneal (i.p.) injection of InCl (3) at a dose 0.625, 1.25, 2.5, 5, or 10 mg/kg b.w. The frequency of micronuclei, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (P/N ratio) and body weight gain were determined 24 h after administration of the InCl(3). In the in vitro micronucleus test, CHL/IU cells were treated continuously for 24, 48, or 72 h in the absence of S9mix (the continuous treatment method) and/or for 6 h with or without S9 mix followed by an 18, 42 or 66 h recovery time (the short time treatment method). The frequency of micronuclei was determined at the end of each culture period. RESULTS: The frequency of micronuclei induced by InCl(3) increased in the in vivo erythroblast-erythrocyte micronucleus test using BALB/c mice at doses of 2.5 and 5 mg/kg b.w. The P/N ratio, a marker of bone marrow toxicity, decreased significantly following the injection of InCl(3). Body weight gain was also inhibited by InCl(3). InCl(3) induced micronuclei in the CHL/IU cell micronucleus test in both the continuous treatment method and the short time treatment method, both with and without S9mix. CONCLUSIONS: These results suggest that InCl(3) has a genotoxic effect on mammalian cells both in vivo and in vitro.