Chronic cadmium treatment induces islet B cell injury in ovariectomized cynomolgus monkeys.
In an attempt to establish a primate model of chronic cadmium (Cd) toxicosis, we ovariectomized cynomolgus monkeys and treated with CdCl2 by repeated intravenous injections for 13 to 15 months. The animals showed an increase in blood glucose from Month 10 and a decrease in blood insulin at Month 11of the Cd-treatment. Histopathological examination of the Cd-treated animals revealed islet atrophy with reduction in islet number and vacuolation of the islet cells, whereas there was no remarkable change in the acinar cells of the exocrine pancreas. In histomorphometrical examination, insulin-positive areas in the islets were significantly decreased, accompanying a relative increase of glucagon-positive areas. Large amounts of Cd accumulated in the pancreas, and metallothionein (MT), a Cd binding protein, was localized in the islets of Cd-treated animals. The present study demonstrated that the chronic intravenous injection of Cd to cynomolgus monkeys induced the accumulation of the metal in the pancreas, degeneration of islet B cells and the diabetic clinical signs. Therefore the islet B cell is one of the major targets of the chronic Cd poisoning in monkeys.
Kurata
Yoshimasa
Y
Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Katsuta
Osamu
O
Doi
Takuya
T
Kawasuso
Takeshi
T
Hiratsuka
Hideaki
H
Tsuchitani
Minoru
M
Umemura
Takashi
T
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity; D002105:Cadmium Poisoning / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008252:Macaca fascicularis; D008668:Metallothionein / Q000378:metabolism; D008992:Monkey Diseases / Q000139:chemically induced* / Q000473:pathology; D010052:Ovariectomy; D011897:Random Allocation
D001786:Blood Glucose; D007328:Insulin; D002104:Cadmium; D005934:Glucagon; D008668:Metallothionein