A Review of the Biosynthesis and Structural Implications of Insulin Gene Mutations Linked to Human Disease

The discovery of the insulin hormone over 100 years ago, and its subsequent therapeutic application, marked a key landmark in the history of medicine and medical research. The many roles insulin plays in cell metabolism and growth have been revealed by extensive investigations into the structure and function of insulin, the insulin tyrosine kinase receptor (IR), as well as the signalling cascades, which occur upon insulin binding to the IR. In this review, the insulin gene mutations identified as causing disease and the structural implications of these mutations will be discussed. Over 100 studies were evaluated by one reviewing author, and over 70 insulin gene mutations were identified. Mutations may impair insulin gene transcription and translation, preproinsulin trafficking and proinsulin sorting, or insulin-IR interactions. A better understanding of insulin gene mutations and the resultant pathophysiology can give essential insight into the molecular mechanisms underlying impaired insulin biosynthesis and insulin-IR interaction.

Automated summary

The discovery and therapeutic application of insulin hormone over 100 years ago was a significant breakthrough in medicine and medical research. Extensive investigations into the structure and function of insulin, insulin tyrosine kinase receptor (IR), and the signalling cascades upon insulin binding have revealed its multiple roles in cell metabolism and growth. This review discusses insulin gene mutations causing disease and their structural implications, with over 70 mutations identified from more than 100 studies. Understanding these mutations and their pathophysiology is crucial in deciphering the molecular mechanisms of impaired insulin biosynthesis and insulin-IR interaction.