Role of metallothionein and cysteine-rich intestinal protein in the regulation of zinc absorption by diabetic rats.
Hyperzincuria and low Zn absorption in diabetic animals and humans have prompted speculation that diabetics are more susceptible to Zn deficiency. There is little information, however, describing the effects of diabetes on the biochemical mechanisms of intestinal Zn transport. We evaluated Zn absorption in streptozotocin-induced diabetic rats based on a model of Zn transport in which cysteine-rich intestinal protein serves as an intracellular carrier that is inhibited by metallothionein (MT). Apparent absorption and retention of Zn and Cu in rats fed a purified diet were measured in a balance study 15-17 d after induction of diabetes. The rate of 65Zn absorption from isolated intestinal segments, molecular distribution of 65Zn in mucosal cytosol, and tissue MT levels were measured on d 20-22. Food consumption, and thus Zn and Cu intake, by diabetic rats was twice that of controls. Although fractional absorption (percent) of Zn and Cu was lower in the diabetic rats, net absorption (micrograms/100 g body weight/d) was higher. The higher net absorption in the diabetic group was offset, however, by higher urinary excretion, so that Zn and Cu retention was similar in both groups of animals. Low fractional absorption is attributable to the down-regulation of intestinal Zn transport, as indicated by the lower rate of 65Zn absorption from isolated intestinal segments in the diabetic rats. Down-regulation of intestinal transport is in turn attributable to higher concentrations of intestinal MT, which resulted in more 65Zn in the mucosal cytosol bound to MT, an inhibitor of Zn transport, and less to cysteine-rich intestinal protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Escobar
O
O
Department of Pediatrics, Louisiana State University School of Medicine, New Orleans 70112, USA.
Sandoval
M
M
Vargas
A
A
Hempe
J M
JM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D003300:Copper / Q000097:blood / Q000493:pharmacokinetics*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D007408:Intestinal Absorption / Q000502:physiology*; D060588:LIM Domain Proteins; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D015032:Zinc / Q000097:blood / Q000493:pharmacokinetics*
D001786:Blood Glucose; D002352:Carrier Proteins; C071434:Crip1 protein, rat; D060588:LIM Domain Proteins; D013311:Streptozocin; D003300:Copper; D008668:Metallothionein; D015032:Zinc