INTESTINAL ENDOGENOUS ZINC: ROLE FOR METALLOTHIONEIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Zinc (Zn) deficiency has been amply demonstrated on a global basis, as have the adverse implications of Zn deficiency on health. Zn has many important functions in the body, and yet much remains to be learned about exactly how Zn is used. Healthy individuals balance the amount of Zn in their bodies by regulating absorption of Zn from food into the gut and by controlling the release of zinc back into the intestine for excretion in feces. Most research has focused on zinc absorption by the gut. This study will better characterize the physiology of and factors affecting zinc secretion into the intestine. An improved understanding of the ways in which the body usually achieves proper zinc balance may help to ultimately treat and/or prevent Zn deficiency. This study will investigate if a protein, metallothionein, controls Zn secretion into the intestine. Based on experimental data from animal studies and our own preliminary data, we hypothesize that the amount of metallothionein in secretions from the pancreas into the small intestine is directly related to the amount of Zn in these secretions. This study will also evaluate whether the amount of metallothionein in secretions from the pancreas changes when the amount of zinc absorbed from food changes and when the Zn load in the body changes. Healthy adults aged 20-50 will be recruited from the Denver metro area. We will study 10 subjects on a diet with Zn levels similar to their usual diets. Subjects will then be randomly assigned to a Zn restricted or supplemented diet. Before and after they begin their assigned diet, subjects will spend 2 days in the GCRC, where a small tube will be inserted into each subject's mouth and advanced down his/her throat to his/her intestine. This tube will be used to suck out secretions that we will then analyze. All subjects will also receive some special forms of Zn on different days in the study. These will help us to measure Zn amounts in the secretions collecte