1. Diabetes and Stem Cells

2. Diabetes Year 2000 – Estimated 171 million people Year 2013 – Estimated 343 million people Class as an epidemic

3. Diabetes Type I- Immune system attacks pancreas – Insulin-producing pancreatic β cells destroyed Type II- Secondary factors destroy insulin producing cells – E.g. genetic predisposition Type I (childhood) Diabetes vs. Type I Diabetes

4. Severe organ complications associated with the disease – Blindness – Autonomic dysfunction – Increased risk of peripheral vascular disease cerebrovascular disease cardiovascular disease

5. Diabetes Current treatment = artificial insulin supplementation Impacts lifestyle as well as health – Need a new approach Stem cells

6. The Optimal Diabetes Therapy Artificial β- Cells – Glucose dependant insulin release Unlimited cell supply Functional consistency Inexpensive

7. The Answer Stem cells can divide into any cell line – Unlimited cell supply – Low cost K-cells show similar characteristics to pancreatic β- cells – Naturally secrete insulin in response to glucose Stem cells in conjunction with K-cells

8. Timothy Kieffer’s Research K cells natural role is to produce a hormone in response to cellular concentration of glucose – Hormone= GIP hormone GIP is made by reading the information from the GIP gene and transcribing this into the GIP hormone – The process first starts at a region on the gene called the promoter Want to reprogram the promoter on GIP gene to make insulin instead of GIP hormone

10. Timothy Kieffer’s Research In-vitro testing: – Determine if possible to reprogram the GIP promoter to produce insulin instead of the GIP hormone Insert the preproinsulin (immature insulin) into the GIP gene just after the promoter = GIP/ insulin transgene – If so, determine if the expression of insulin is targeted to K Cells If in-vitro testing is successful then need to test in live hosts (in-vivo testing)

11. Timothy Keiffer’s Research In-vivo testing: – Use mice hosts – Inject GIP/human insulin transgene into the fertalized embryos so that the mice produce this type of insulin and not their own Mice now called transgenic mice – Recorded that transgenic mice had human insulin expression

12. Timothy Kieffer’s Research Results: – Test group mice= transgenic mice that have the GIP/human insulin gene – Control group mice= “normal” mice – Both groups were administered a β-blocker that makes the insulin producing pancreatic β cells non functioning Mice represent diabetics

13. Timothy Kieffer’s Research The transgenic mice were able to dispose of glucose, even though they have no pancreatic β cells Control mice developed diabetes

14. Recent Research Scientists have developed a mechanism for regulating the amount of insulin the K cells are producing if ever need be Development of a safe gene delivery strategy to the K cells