This week we profile a recent publication in Diabetes from Dr. Gregory Morton (left)
and Chelsea Faber (right) at the UW Medicine Diabetes Institute.
Can you provide a brief overview of your lab’s current research focus?
Diabetes is a major public health concern that increases the risk of cardiovascular disease and is a leading cause of blindness, amputation and kidney failure. The mission of the Morton laboratory is to understand the role of the brain in the control of blood sugars and determine how defects in this system contribute to insulin resistance and diabetes. Specifically, our laboratory, in collaboration with Dr. Michael Schwartz at the University of Washington (UW), examines how the brain senses and responds to hormonal and nutrient-related input from the periphery and engages neurocircuits that regulate blood sugar levels. In order to identify and functionally characterize these neurocircuits, we employ a neuroscience technique known as optogenetics, which uses light to turn on or turn off specific neurons in defined brain areas in freely moving animals. With the information obtained from these studies, we can better understand how the brain maintains glycemic control, with the ultimate goal of identifying novel targets in the brain that may be used to prevent, treat or cure diabetes.
What is the significance of the findings in this publication?
The brain contains many different regions that mediate a vast array of functions. One region of the hypothalamus, for example, is the ventromedial nucleus (VMN) which is implicated not only in glycemic control, but also mediating “fight or flight” responses during fearful or stressful stimuli. Work spearheaded by Chelsea Faber, a Molecular Medicine Mechanisms and Disease (M3D) graduate student at the UW, investigated whether these glycemic vs. behavioral effects could be dissociated from one another, and if we could identify cell types or neurocircuits that specifically mediate the glycemic effects. Using an optogenetics approach in mice, our findings identify a novel VMN neurocircuit that projects to a forebrain region called the anterior bed nucleus of the stria terminalis (aBNST) that raises blood glucose levels and plays an important role in the physiological response to hypoglycemia. In contrast, a separate VMN neurocircuit that projects to the periaqueductal gray (PAG) mediates behavioral “fight or flight” responses. Further insight into these VMN neurocircuits will inform our understanding of both hypoglycemia and its complications in patients with diabetes and mechanisms underlying the “fight or flight” response and other defensive behaviors.
What are the next steps for this research?
Hypoglycemia is an important and frequently encountered complication of diabetes treatment. One episode of hypoglycemia increases cardiovascular disease risk and further increases the risk of subsequent hypoglycemic episodes. A better understanding of this neurocircuit may help identify future strategies for prevention of both insulin-induced hypoglycemia and hypoglycemia unawareness, two of the most common and costly complications of diabetes treatment. Moreover, such approaches can be utilized to identify other novel neurocircuits that, when activated, lower blood glucose levels in rodent models of diabetes.
This research was funded by:
This work is part of a collaborative effort with other members of the UW Medicine Diabetes Institute and is funded by the National Institutes of Health. More information on the research can be found at: depts.washington.edu/doce/
