Zinc status In patients with Type I diabetes is significantly lower than healthy controls. Whether zinc supplementation can prevent the onset of Type I diabetes Is unknown. Recent studies have suggested that the generation of reactive oxygen species (ROS) Is a cause of II cell death leading to Type I diabetes. In addition, we found that activation of NFKB (a ROS-sensltlve transcription factor that regulates immune responses) may be the key cellular process that bridges oxidative stress and the death of 11 cells. Zinc is a known antioxidant in the Immune Key words: reactive oxygen species; free radicals; zinc; NFKB; diabetes; alloxan; streptozotocln T ' "'" ' ype I diabetes is a devastating disease that occurs .~l ost often in children or young adults.~hi s d.isease IS characterized by the profound destruction of the 13 cells of the islets of Langerhans in the pancreas, resulting in

Objectives: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. Design: Eighteen healthy women participated in a three-way cross-over study for ®ve week periods separated by seven week washout periods, diets were assigned in random order. Subjects: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3a3, 3a2, 4a3, and 4a2). Intervention: During the ®rst week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10 en% polyunsaturated fat and 14 en% monounsaturated fat. Followed by test diets with 19 en% saturated fat (including 14 en% test saturated fatty acid), 3 en% polyunsaturated fat, and 14 en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. Results: Mean concentrations of serum total, esteri®ed and LDL cholesterol were signi®cantly lower after 18:0 than after 16:0 (n 16 ± 18, P`0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect.Receptor-mediated degradation of 125 I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n 16 ± 18, P 0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. Conclusions: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride, was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype in¯uenced the cholesterolemic response particularly when diets high in 16:0 were eaten.

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.

Many risk factors can trigger the development of insulin‐dependent diabetes mellitus (IDDM). The induction of IDDM in vivo is strongly associated not only with the generation of reactive oxygen species but also with the activation of the transcription factor nuclear factor‐κB (NF‐κB). The purpose of this study was to determine the role of NF‐κB activation in diabetogenesis. Alloxan, a diabetogenic compound that causes diabetic conditions by selectively killing the insulin‐producing pancreatic β‐cells, was used as a model chemical compound to induce diabetes. We show here that the injection of alloxan in mice rapidly and specifically induced the activation of NF‐κB in the pancreas. Intravenous administration of synthetic oligodeoxynucleotides, which are exact copies of the DNA binding site of NF‐κB (NF‐κB decoy), given before the alloxan injection, effectively blocked pancreatic NF‐κB activation in mice and subsequently prevented pancreatic cell death, restored insulin secretion, and abolished hyperglycemia. Injection of scrambled NF‐κB decoy oligodeoxynucleotides to mice had no effect on alloxan‐induced diabetic conditions. These results demonstrate that NF‐κB activation in the pancreas is required for the induction of chemically induced diabetes by alloxan.

Medium-chain triglycerides (MCT) are often used in specialized formula diets or designer fats because of their special properties. Yet their influence on lipid metabolism is not completely understood. In this two-period cross-over study, the effects of MCT (8:0 + 10:0) in contrast to a similar saturated fatty acid (12:0) were compared. Eighteen healthy women ate a baseline diet [polyunsaturated (PUFA)/saturated fat = 0.9] for 1 wk. Then, they consumed test diets (PUFA/saturated fat = 0.2) for 4 wk. Monounsaturated fat and cholesterol were constant in baseline and treatment diets. MCT and 12:0, substituted for part of the PUFA, provided 14 energy (en)% of the test diets. In comparison to the PUFA baseline diet, a 16% increase in mean serum low density lipoprotein (LDL)-cholesterol (C) on the 12:0 diet was accompanied by a 21% decrease in mean receptor-mediated degradation of LDL by freshly isolated mononuclear cells (MNC) in vitro. The MNC assay theoretically gives an indication of receptor-mediated degradation of LDL. In contrast, the MCT diet raised mean receptor-mediated degradation of LDL by 42%, a finding out of line with the mean 11% increase in serum LDL-C. Perhaps MCT, by increasing the rate of LDL-C production, overcame the rate of LDL-C clearance. The 12:0 diet enhanced some factors involved in reverse cholesterol transport (e.g., high density lipoprotein fractions) while MCT had a different or less pronounced effect. The overall effects of MCT on cholesterol metabolism may or may not be desirable, whereas those of 12:0 appear largely undesirable as previously reported.