The recent development of molecular biology enables us to identify three abnormal insulins (insulin Chicago, insulin LosAngeles and insulin Wakayama). In Japan, three pedigrees in which affected individuals secrete [Leu^A3] insulin (insulin Wakayama) have been identified. In each family, hyperinsulinemia associated with an abnormally elevated insulin to C-peptide molar ratio was demonstrated to occur in an autosomal dominant pattern of inheritance. In accordance with in vivo observations, semisynthetic [Leu^A3] insulin demonstrated reduced in vitro receptor binding and biological activity relative to the human standard. The development of diabetes mellitus in affected family members was not uniform, was influenced by aging, and was different among families. Patients with impaired glucose tolerance demonstrated reduced insulin secretory reserve. Some of these features are thought to resemble the nature of noninsulin dependent diabetes mellitus (NIDDM).
Therefore, insulin Wakayama may be an useful model for the study of the development of NIDDM.