| Description |
The demand for therapeutic insulin is growing constantly as the number of people with either type 1 and type 2 diabetes steadily increases. Approximately 400 million diabetic patients worldwide receive treatment to maintain blood glucose levels within the normal healthy range. In insulin-based injectable therapeutics, there are four different types: rapid-, short-, intermediate- and long-acting insulin. They have been used to regulate glycemia in many diabetic patients. However, one main problem of current injectable insulin therapeutics is that decreasing blood sugar levels can occur whether or not patients need to control glycemia after the insulin is injected, and this can eventually lead to hypoglycemia. Thus, glucose-responsive insulin, which is an advanced new insulin therapeutic, is being developed to regulate glycemia based on the blood glucose level. In this way, the risk of hypoglycemia as well as the treatment of hyperglycemia can be reduced. Chapter 1 provides general information about insulin and diabetes. Additionally, two major insulin synthesis methods are discussed. Chapter 2 reports that a phenylboronic acid-modified insulin glargine derivative has glucose-dependent behavior in vivo due to glucose-dependent differences in solubility. The chemical synthesis and bioactivity of this insulin molecule are demonstrated. In addition, the results of a glucose clamp study and the insulin tolerance test performed in rats are reported. Chapter 3 focuses on the biosynthesis of the insulin molecule. Preproinsulin was produced successfully in E. coli, and the purification process was optimized. Chapter 4 discusses the conclusions generated iv from this project and future directions. The primary future direction involves completing the biosynthetic process, including the refolding and formation of mature insulin to produce the final product. |
