Non-peptidyl insulin mimetics as a potential antidiabetic agent

•Benzoquinone analog is identified as an activator of insulin receptor tyrosine kinase.•Modification of this molecule provided potent and specific activators of receptor.•Vanadium mimics insulin actions by inhibiting protein tyrosine phosphatases.•Specific activators of protein tyrosine phosphatase 1B have been designed.•Identification of such small molecules provided an opportunity to replace insulin. Insulin has an important role in the maintenance of blood sugar. It is the only available therapeutic agent for the treatment of type 1 diabetes mellitus and there is a dire need for an oral substitute. Different categories of compounds including mono and di substituted benzoquinones, vanadium based compounds and natural products have been reported to cause insulin-like effects either by increasing phosphorylation of insulin receptor (IR) or inhibiting the protein tyrosine phosphatases. This review summarizes the development of various insulin mimetics with special emphasis on their structure–activity relationships and various biological actions they produce.