Zinc (Zn) deficiency is a public health problem of global proportions, and is of clinical significance in many disease states. Our understanding of Zn homeostasis remains, however, far from complete, especially in the regulation of the major route of loss of Zn from the body: secretion into the intestine and excretion via the feces. A large database from human whole body Zn metabolism studies now indicates that endogenous fecal Zn is related to the amount of absorbed dietary Zn, to Zn """"""""status"""""""" of the host, and to the size of rapidly exchanging zinc pools (EZP). The proposed pilot studies examine the potential role of metallothionein (MT) in pancreaticobiliary secretions as a modulator of Zn secretion into the human gastrointestinal tract. Metallothionein is proposed for this process on the basis of animal data indicating that the pancreas is a site of MT gene expression and synthesis that is responsive to parenteral and enteral Zn, and that MT is a normal constituent of pancreaticobiliary secretions.
The specific aims are to determine in pancreaticobiliary secretions if: (1) the amount of MT is directly related to endogenously secreted Zn; (2) the amount of MT is responsive to changes in dietary Zn intake, absorbed Zn, and EZP size; and (3) the amount of MT is increased with """"""""stress"""""""" in pancreaticobiliary secretions, and thereby associated with increased endogenous Zn secretion. Proposed methods include gastroduodenal intubation and aspiration of pancreaticobiliary secretions, in which MT and Zn will be measured, and Zn stable isotope techniques by which key variables of Zn homeostasis will be measured. One study will be conducted in 10 normal adult subjects on their habitual Zn intake and repeated after either Zn restriction or Zn supplementation. A second study will examine the effects of cytokine stimulation by interferon-7 on MT and endogenous Zn secretion while Zn intake is constant. Measurement of MT will be made using the well established but indirect cadmium-hemoglobin affinity assay and by a proposed new immunoassay, which will yield more accurate and precise measurements of human MT. Proposed data analyses include correlations between total flow of MT and endogenous Zn to determine temporal and quantitative relationships between these 2 variables within and between subjects; stepwise multiple regression to examine effects on MT and variables of Zn homeostasis; and paired comparisons between MT and endogenous Zn secretion on habitual Zn intake and either Zn restricted or supplemented diets, and before and after interferon-y administration.
| Tran, Cuong D; Miller, Leland V; Krebs, Nancy F et al. (2004) Zinc absorption as a function of the dose of zinc sulfate in aqueous solution. Am J Clin Nutr 80:1570-3 |
