Researchers Offer Inspiration and Advice for World Diabetes Day

Female scientists paved the way for many breakthroughs in diabetes research labs around the world.1,2 In recognition of the World Diabetes Day 2017 theme: “Women and Diabetes,” we asked leading female diabetes researchers Dr. Darleen Sandoval, Dr. Lori Sussel, and Dr. Christine Doucette to share their career inspiration and advice for aspiring investigators.

Headshots of Drs. Sandoval, Sussel and Doucette

What or who inspired you to pursue a career in diabetes research?

Dr. Sandoval: It was my interest in metabolism that led me to diabetes research. I loved my biochemistry classes when we were learning about metabolic pathways. I also had an excellent co-advisor, Mike Pagliassotti, for my PhD who inspired me and directed me to this field.

Dr. Sussel: I have always been intrigued about how cell lineage decisions are made during fetal development.  When I discovered that diabetes could be cured by replacing or restoring the function of the insulin-producing β-cell, I decided that I wanted to figure out the regulatory networks that would allow us to generate or regenerate those cells. That was 20 years ago and I am still working on the same question. Amazingly, we are a lot closer to answering this question, but there is still much we do not know.

Dr. Doucette: While I was happy with the work that I had done during my PhD, I felt the need to do research that was more directly relevant to human health for my Postdoctoral Fellowship. My uncle, who was living with T2D, had developed major complications. It wasn’t long before he passed away. I wished that I could use my education and training in research to help him and others living with diabetes. I eagerly applied for a Postdoctoral Fellowship position in diabetes research at Dr. Michael Wheeler’s lab at the University of Toronto. Dr. Wheeler took a chance on me and offered me the position, starting my career in the field.

Why is your research important and what are the possible real-world applications?

Dr. Sandoval: Overall, we are interested in how the gut and brain communicate to regulate glucose metabolism. Much of the work we do is focused on “reverse translation”, meaning that we take clinical findings and observations and try to understand mechanisms of action. Bariatric surgery which rearranges gut anatomy, is our most effective strategy to induce weight loss as well as the only intervention that can cause resolution to T2D. Some of our work is focused on understanding why these surgeries are so effective to find more simplistic strategies for treating obesity and T2D.

Dr. Sussel: Our research on the regulation of cell fate decisions is important for understanding the precise molecular mechanisms behind the process. In theory, these studies should allow us to learn enough to easily generate any cell type in the body. A particularly relevant application of this research is that we are learning how to generate and maintain the identity of functional β-cells in the mouse model system. Ultimately, this knowledge is being used to generate unlimited sources of functional human β-cells from alternative sources for cell replacement therapies.

Dr. Doucette: My research program is currently exploring metabolic regulators of 24 hour cycles of insulin secretion capacity such as the circadian clock and the role of a single nucleotide polymorphism in the hepatocyte nuclear factor-1 alpha gene (“HNF-1aG319S”), which strongly associates with youth-onset T2D in an Indigenous First Nations population in the Canadian province of Manitoba. I envision that my research will lay the foundation of new knowledge upon which future novel diabetes interventions and therapies can be developed.

What has been the most important breakthrough for you in your research?

Dr. Sandoval: After a meal, the gut secretes many peptides into the circulation and these peptides are thought to be essential for regulating glucose metabolism and feeding behavior. We are particularly interested in one of these peptides, glucagon-like peptide-1 (GLP-1). GLP-1 is thought to be secreted into the circulation after a meal to specifically regulate insulin secretion. However, our recent findings suggest that intestinal sources of GLP-1 have little to do with glucose homeostasis and instead pancreatic sources of GLP-1 do. This work is dogma-challenging and there is a lot of work to be done to understand how this system would work.

Dr. Sussel: I would like to say our most surprising and exciting scientific breakthrough was when we generated mutant mice with islets filled with cells producing the orexigenic hormone ghrelin instead of insulin. We still don’t completely understand the importance of this lineage relationship or what ghrelin is doing in the islet. More recently, like other groups, our research has revealed remarkable plasticity and heterogeneity in adult islet cell lineages, which changes the way we think about islet dysfunction in diabetes and possible treatments.

Dr. Doucette: For me, I have had two significant breakthroughs in my career that have changed the trajectory of my research. My first breakthrough came while I was researching the role of uncoupling protein 2 (UCP2) in the β-cell in Dr. Wheeler’s lab. We discovered that UCP2 expression is regulated in a circadian manner and controls the capacity for insulin secretion in a temporal manner over 24 hours. More recently, my lab at the University of Manitoba worked with Dr. Barbara Triggs-Raine to develop a successful mouse model for studying HNF-1aG319S. Our mouse model will allow us for the first time to study in vivo how the G319S variant affects β-cell function, metabolic health, and gene-environment interactions.

Do you have any advice for young investigators interested in diabetes research?

Dr. Sandoval: There are many things I have learned along the way, but the key things that I would emphasize are work hard and have perseverance. There is just no substitute for hard work. Science can be difficult at times. Papers and grants get rejected. You can’t take it personally or let it get you down. Bottom line is, you just have to keep going!

Dr. Sussel: Both type 1 diabetes and type 2 diabetes are complex diseases. There is still a lot to learn and discover using a variety of model organisms and understanding basic biological systems.

Dr. Doucette: Be patient, but persistent while maintaining flexibility. Academic freedom is a wonderful thing and sometimes the questions you set out to answer may lead you to a completely different and far more interesting question. Be flexible and follow where your research takes you!

Dr. Sandoval, Dr. Sussel, and Dr. Doucette’s inspiration and advice for World Diabetes Day 2017 offer hope for future researchers and those suffering from type 1 and type 2 diabetes. These passionate and dedicated scientists are making an impact in the diabetes research field every day. Their commitment to advancing scientific breakthroughs throughout their careers is both a testament to those who inspired them and a source of encouragement for young investigators to follow.

Be sure to also check out these publications and further explore the work of Drs. Sandoval, Sussel and Doucette.

Dr. Sandoval

  1. Hutch and Sandoval (2017). The role of GLP-1 in the metabolic success bariatric surgery. Endocrinology. 2017 Oct 9. PMID: 29040429.
  2. Seeley, Chambers, Sandoval (2015). The Role of Gut Adaptation in the Potent Effects of Multiple Bariatric Surgeries on Obesity and Diabetes. Cell Metab. 3;21(3):369-78. 2015. PMID: 25662404.
  3. Sandoval and D’Alessio (2015). Physiology of Proglucagon Peptides: The role of glucagon and GLP-1 in health and disease. Physiology Reviews. 95(2):513-48. 2015. PMID: 25834231.

Dr. Sussel

  1. Gutierrez, Gromada, Sussel (2017). Heterogeneity of the Pancreatic Beta Cell. Front Genet. 2017 Mar 6;8:22. doi: 10.3389/fgene.2017.00022. eCollection 2017. PMID: 28321233.
  2. Romer and Sussel (2015). Pancreatic islet cell development and regeneration. Curr Opin Endocrinol Diabetes Obes. 2015 Aug;22(4):255-64. PMID: 26087337.
  3. Prado, Pugh-Bernard, Elghazi, Sosa-Pineda, Sussel (2004). Ghrelin cells replace insulin-producing cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2924-9. PMID: 14970313.

Dr. Doucette

  1. Seshadri, Jonasso, Hunt, Xiang, Cooper, Wheeler, Dolinsky, Doucette (2017). Uncoupling protein 2 regulates daily rhythms of insulin secretion capacity in MIN6 cells and isolated islets from male mice. Mol Metab. 2017 Apr 27;6(7):760-769. PMID: 28702331.
  2. Jonasson, Wicklow, Seller, Dolinsky, Doucette (2015). Exploring the role of the HNF-1αG319S polymorphism in β cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models. Biochem Cell Biol. 2015 Oct;93(5):487-94. PMID: 26176428.
  3. Doucette and Rosen (2014). Current Protocols in Mouse Biology. Curr Protoc Mouse Biol. 2014;2014. PMID: 25599005.

References

  1. Yalow and Berson (1960). Immunoassay of Endogenous Plasma Insulin in Man. J Clin Invest. 1960 Jul;39(7):1157–1175. doi: 10.1172/JCI104130. PMCID: PMC441860.
  2. Adams, et al (1969). Structure of Rhombohedral 2 Zinc Insulin Crystals. Nature. 01 November 1969;224:491 – 495. doi:10.1038/224491a0. PMID: 4508138.