Chemistry and biochemistry of insulin-mimetic vanadium and zinc complexes. Trial for treatment of diabetes mellitus

The number of patients suffering from diabetes mellitus (DM), which is a chronic metabolic disorder and mainly classified as either insulin-dependent type I or non-insulin-dependent type 2, is increasing throughout the world. The sequence of DM progression makes this disease a major health risk in regard to microvascular disease that leads to kidney failure, blindness, and nerve damage as well as macrovascular disease that leads to amputations, cardiovascular disease, and stroke. To treat DM, several types of insulin preparations and synthetic drugs for type I and type 2 DM, respectively, are in clinical use. However, there are several problems concerning the insulin preparations and synthetic drugs, such as physical and mental pain due to daily insulin injections and defects involving several side effects, respectively. Thus, the disease demands extraordinary effects to define pathobiochemical pathways and strategies for prevention and to find new therapeutic approaches. For this purpose, oxovanadium(IV) (vanadyl, VO2+) and zinc(II) containing complexes have been explored as treatments for both types of DM. This article reviews the current state of research on insulin-mimetic and antidiabetic metal complexes, with special focus on paramagnetic vanadyl and diamagnetic zinc(II) complexes with different coordination modes, together with possible reaction mechanisms. New drug delivery systems involving enteric-coated capsulation and a biopolymer are also reviewed.