Research Description
The pancreatic beta-cells express and secrete insulin to mediate blood glucose regulation. During pregnancy, beta-cells need to adapt to the increased metabolic demand of the fetus. To achieve this, beta-cells become larger and proliferate, while producing and secreting more insulin. Defective metabolic adaptations manifest as gestational diabetes (GDM), which correlates with increased maternal and fetal-neonate health risks, which extend beyond birth. Therefore, it is essential to understand the mechanisms by which beta-cells adapt during pregnancy. Lactogens such as placental lactogens and prolactin, signal via the prolactin receptor (PRLR) expressed by the beta-cells to mediate many beta-cell adaptations to pregnancy. We know that other lactogen-responsive tissues in the body, such as the mammary glands, adapt to pregnancy using epigenetic mechanisms. Epigenetic regulation, which controls whether DNA sequences can be accessed to regulate gene expression, can be transient or long lasting. STAT5, which is regulated by PRLR signaling, has been associated with long-term epigenetic changes in the mammary glands and the hypothalamus, a region in the brain which regulates many physiological processes, including hunger, mood, and sleep. This led to the hypothesis that: PRLR signaling mediates epigenetic changes in beta-cells during pregnancy. Furthermore, this study will answer: 1) if PRLR signaling acts via similar mechanisms in humans and mice, 2) whether known PRLR-regulated genes are involved in epigenetic remodeling, and 3) if PRLR-mediated epigenetic changes last beyond birth. Together, it is important to understand the mechanisms by which PRLR signaling regulates beta-cell adaptations and how it contributes to physiology and disease.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?We study how the insulin-producing beta-cells adapt to pregnancy and postpartum. Defective metabolic adaptations manifest as gestational diabetes (GDM) which is known to increase maternal and fetal-neonate health risks, even beyond birth. Many beta-cell adaptations to gestation, are mediated by lactogen signaling. Lactogens such as placental lactogen and prolactin, promote beta-cell proliferation and increase the production and secretion of insulin. We want to understand the mechanisms by which lactogen signaling contribute to beta-cell adaptations to pregnancy and postpartum and how these contribute to normal physiology and disease. Deeper beta-cell biology knowledge can lead to increased understanding of the genetic, environmental, and mechanistic underlying causes which can lead to better targetted approaches to treat diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Our work seeks to understand the underlying mechanisms by which beta-cells adapt to pregnancy and postpartum. To adapt to the increased metabolic demand due to pregnancy beta-cells proliferate and increase their production and secretion of insulin. Understanding the mechanisms of normal physiological adaptations of beta-cells to pregnancy can allow us to 1) identify how defects in these adaptations lead to disease and 2) allow us to target pathways to improve beta-cell function in a disease state.
Why important for you, personally, to become involved in diabetes research? What role will this award play?I am passionate about pancreatic islet biology, its functions and its implications in physiology and disease. The Postdoctoral Fellowship Award from ADA will provide funds and support my efforts to this project, which is a crucial step to achieve my long-term goal to become an independent researcher and has only furthered my desire to understand the molecular and cellular underpinnings of diabetes as a metabolic disease.
In what direction do you see the future of diabetes research going?Diabetes is a complex disease, which can stem from dysregulation of one or many molecular pathways. I believe it is crucial to understand the underlying causes both at the cellular and systemic level in order to prevent, treat or potentially cure this disease. Therefore, the future of diabetes relies on the collaboration of researchers and clinicians to narrow the gap of knowledge and its implications for patient care.