The role of the pancreas in intestinal zinc secretion in metallothionein-null mice.
The distribution and excretion of endogenous Zn, including the role of the pancreas, were examined in fasted MT+/+ and MT-/- mice. At 3 and 6 h after receiving 65Zn tracer by subcutaneous injection, 65Zn levels were compared in tissues of MT+/+ and MT-/- mice. 65Zn levels were significantly higher in the liver and pancreas of the MT+/+ mice, whereas in the MT-/- mice, 65Zn levels were significantly higher in muscle, skin, and most of the gastrointestinal tract other than the stomach and upper small intestine. In MT-/- mice, 3% of the injected 65Zn was recovered in the luminal contents of the small intestine over 3-6 h, compared with <1.5% in the MT+/+ mice. A loading dose of Zn (150 microg, s.c.) sufficient to raise the plasma Zn concentration by fourfold to fivefold in both MT+/+ and MT-/- mice resulted in similar increases in pancreatic Zn levels in each genotype, although more Zn appeared in the lower small intestine of MT-/- mice. Pancreatectomy decreased the level of 65Zn in the small intestine of MT-/- but not MT+/+ mice. Longer-term studies over 4 days demonstrated few differences in tissue 65Zn between MT+/+ and MT-/- mice, with the exception of the pancreas, where 65Zn retention after fasting in MT-/- mice was half that of MT+/+ mice. MT-/- mice also had significantly lower Zn concentrations in the pancreas. Fecal excretion of 65Zn in MT-/- mice was greater than that of MT+/+ mice in the first 24 h (24.7 vs. 18.2% of injected dose; p < 0.05). Besides metallothionein (MT), there were no significant differences in the molecular weight distribution of Zn binding ligands in the lumen of the small intestine between MT+/+ and MT-/- mice. Mice lacking MT I and II lose more endogenous Zn into the gut because of a relative failure of the pancreas to retain Zn. However, increased Zn secretion via the small intestinal mucosa may also contribute to intestinal Zn loss in MT-/- mice.
Rofe
A M
AM
Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, Australia. Allan.Rofe@imvs.sa.gov.au
Winters
N
N
Hinskens
B
B
Philcox
J C
JC
Coyle
P
P
D000818:Animals; D005215:Fasting / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D007421:Intestine, Small / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000502:physiology* / Q000601:surgery; D010180:Pancreatectomy; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D008668:Metallothionein; D015032:Zinc