ANALYSIS OF THE POSSIBLE PROTECTIVE ROLE OF METALLOTHIONEIN IN STREPTOZOTOCIN-INDUCED DIABETES USING METALLOTHIONEIN-NULL MICE

In order to clarify a possible protective role of metallothionein (MT) in the development of streptozotocin (STZ) - caused insulin-dependent diabetes mellitus (IDDM) and its mechanisms, we studied whether MT is effective for protection against STZ-caused IDDM by utilizing MT-null (isoforms MT-I and II) transgenic mice. It was found that Zn pretreat ment (1 mg/kg body weight as ZnSO4) has a unique inhibitory effect on IDDM development in MT-null mice in contrast to no marked effect in co ntrol (C57BL/6J) mice, suggesting that Zn ions free from MT molecules exerted this protective effect. The highest Zn dose (10 mg/kg body wei ght) fully suppressed development of hyperglycaemia in both types of m ice. Pretreatment with Zn partially led to recovery of superoxide dism utase activities in the liver and pancreas in which STZ administration suppressed superoxide dismutase activity in both types of mice. The p resent study suggests that Zn plays an important role in the pathogene sis of IDDM, although a possible involvement of MT in the protection o f STZ-caused IDDM cannot be completely negated.