1. Co-Mentors Dr. Melissa Brown, Phd, RD Dr. Alan Schneyer, Phd

2.   Background on T1D & T2D & Significance  Mechanisms for β -cell Replacement  Role of TGF β superfamily member, activin  Specific Aims  Methods  Summary Outline

3.  Diabetes Mellitus  Classification of metabolic disorders characterized by excess glucose in the bloodstream (Ozougwu et al., 2013). Iran, Khan. Type 2 Diabetes: Metabolism Mishaps. 2012.

4.   Autoimmune reaction which leads to destruction of pancreatic B-cells (Ozougwu et al., 2013).  Deficiency of insulin production and insulin secretion (Ozougwu et al., 2013).  Approximately 10% of all cases of diabetes, approximately 20 million people worldwide (American Diabetes Association, 2001). Type 1 Diabetes

5.   Genetic factors, impaired insulin secretion, ↑ insulin resistance and environmental factors ( Kaku,2010).  Involves progressive loss of pancreatic B-cell mass and function (Ozougwu et al., 2013).  Predominant form of diabetes; approximately 90% of all cases of diabetes mellitus (Gonzalez et al., 2009). Type 2 Diabetes

6.  Comparison of diabetes statistics from 2011-2014 Source: (Centers for Disease Control, 2011,2014).

7.  Comparison of economic cost of diabetes in the U.S from 2011-2014 Source: (American Diabetes Association. Economic Costs of Diabetes in the United States, 2008.).

8.   World Health Organization has projected that the incidence of diabetes is set to rise by 64% by 2025  53.1 million citizens will be affected by the disease Significance (Rowley et al., 2012).

9.  Mechanisms for β-cell Replacement  Islet Proliferation: β -cells come from pre- existing β -cells Duct Progenitor  Neogenesis: Formation of new islet cells from progenitor cells (Bonner-Weir et al, Diabetes 2010)   Transdifferentiation (TD): Direct reprogramming of adult islet cell type to another cell fate.

10.  What is the Evidence For a TGFβ Ligand Role in Glucose Metabolism Ligand Islet size  -cell Function Activin A (Florio 2000; Li 2004; Brun 2004 Yamaoka 1998)

11.   Hypothesis: Activin A induces beta cell expansion  Research Objective: Utilize lineage tracing methodology to demonstrate activin A-induced α - to β -cell transdifferentiation that can be used to develop future therapeutics. Hypothesis/Research Objectives/Specific Aims

12.   Cross the FSTL3KO mouse with Glu-Cre+YFP+ mouse  Pancreatectomy to obtain pancreatic islet sections  Histology: Antibody staining for insulin & Glucagon Methods

13. 359-5-islet 10 Glucagon Insulin Yfp Insulin green; Glucagon red Yfp green; Glucagon redYfp green; Insulin red

14.   Preliminary data  Adult islet cell fate more malleable than previously recognized:  - to  -cell or  - to  -cell TD Summary: Sources of New β-cells

15.   Baystate Summer Scholars Program  Dr. Melissa Brown  Dr. Alan Schneyer  Department of Nutrition-Umass Amherst Acknowledgements

16.   Ozougwu, J.C., Obimba, K.C., Belonwu, C.D., Unakalamba, C.B (2013). The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. Journal of Physiology and Pathophysiology, 4(4): 46-57  Iran, Khan. Type 2 Diabetes: Metabolism Mishaps. 2012. Photograph. http://virtualian.ning.com/group/health-tips/forum/topics/what-is-type-2-diabetes#.U9wEQ2NQOco. Web. 1 August 2014.  American Diabetes Association (2001). Diabetes 2001Vital Statistics.  Alexandra, VA: ADA.  Kaku K (2010). Pathophysiology of type 2 diabetes and its treatment policy.  JMAJ, 53(1):41-46  Gonzalez EL, Johansson S, Wallander MA, Rodriguez LA (2009).Trends in the prevalence and incidence of diabetes in the UK: 1996-2005. J. Epidemiol, Community Health. 63: 332-336  Centers for Disease Control and Prevention.National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: U.S. Department of Health and Human Services; 2014. References

17.   Rowley WR, Bezold C. (2012). “Creating public awareness: state 2025 diabetes forecasts. ” Population Health Management. 15.  American Diabetes Association. Economic Costs of Diabetes in the United States in 2007, 2013. Diabetes Care 2008;31:596–615, Diabetes Care. 2013;36(4):1033-1046.  Bonner-Weir, Susan, Wan-Chun Li, Limor Ouziel-Yahalom, Lili Guo, Gordon C. Weir, and Arun Sharma. "β-Cell Growth and Regeneration: Replication Is Only Part of the Story." Diabetes 59.10 (2010): 2340-2348. Print.