ABNORMAL INSULINEMIA

The recent development of molecular biology enables us to identify thr ee abnormal insulins (insulin Chicago, insulin Los Angeles and insulin Wakayama). In Japan, three pedigrees in which affected individuals se crete [LeuA3] insulin (insulin Wakayama) have been identified. In each family, hyperinsulinemia associated with an abnormally elevated insul in to C-peptide molar ratio was demonstrated to occur in an autosomal dominant pattern of inheritance. In accordance with in vivo observatio ns, semisynthetic [LeuA3] insulin demonstrated reduced in vitro recept or binding and biological activity relative to the human standard. The development of diabetes mellitus in affected family members was not u niform, was influenced by aging, and was different among families. Pat ients with impaired glucose tolerance demonstrated reduced insulin sec retory reserve. Some of these features are thought to resemble the nat ure of non-insulin dependent diabetes mellitus (NIDDM). Therefore, ins ulin Wakayama may be a useful model for the study of the development o f NIDDM.