Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from the destruction of the insulin-producing β cells of the pancreas. While treatment options like daily insulin injections or transplantation of whole-pancreas exist, they are associated with significant drawbacks. As a result, there has been great interest in engineering surrogate β cells, both ex vivo and in situ, to replace the function of those cells lost during the progression of the disease. However, the β cell is highly specialized and extraordinarily adept at synthesizing and rapidly secreting the appropriate amount of insulin in response to even small increases in blood glucose levels. Thus, genetic engineering of the “perfect” β cell may prove impossible. In this review, we will detail the features of β cells that make them so proficient at regulating blood glucose and highlight the key features that absolutely must be met by surrogate β cells if they are to be suitable for treatment of T1DM. Then, we will summarize the current approaches used to genetically engineer surrogate β cells, including the overexpression of β cell-specific transcription factors and insulin gene therapy. Along the way, we will discuss the advantages and disadvantages of each approach and review important studies in the field. Lastly, we will discuss important future directions necessary to genetically engineer surrogate β cells with the potential to treat T1DM.
Highlights
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder whereby the insulin-secreting β cells of the pancreas are destroyed
We created a simplified system to control hepatic insulin gene expression by incorporating the Glucose-inducible response elements (GIREs) from the S14 promoter upstream of the albumin promoter, which alone is neither glucose- nor insulinresponsive [49]. We found that this system was able to produce large amounts of glucose-inducible insulin in vitro and promote euglycemia in STZ-induced diabetic rats when fasted or fed ad libitum
The genetic engineering of surrogate β cells provides an exciting alternative to treat T1DM with the potential to meet all of these needs
Summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder whereby the insulin-secreting β cells of the pancreas are destroyed. The most common form of treatment involves injection of synthetic insulin This option is cumbersome and unable to precisely control blood glucose levels. To better imitate normal physiology, specialized insulin pumps, dubbed artificial pancreata, have been developed that use a computer algorithm to deliver insulin [2] [3] or both insulin and glucagon [4] when needed by continuously monitoring blood glucose levels. Using this technology, better glycemic control can be attained compared to traditional insulin therapies. We aim to point out advantages and disadvantages of each approach and propose the minimum requirements necessary for genetically engineering surrogate β cells with the potential to treat T1DM
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
