Committed to understanding the role of the brain in the pathogenesis of obesity and diabetes
The Morton laboratory examines the role of the brain in the regulation of energy balance and glucose metabolism and how defects in this control system may contribute to the development of obesity, insulin resistance and diabetes.
Diabetes is a major health concern that increases the risk of cardiovascular disease and is a leading cause of blindness, leg amputation, and kidney failure. This highlights the need for innovative research to develop and support new approaches to diabetes treatment. Ever since its discovery, research has primarily focused on the pancreatic hormone, insulin in the control of blood glucose levels. This research effort has provided clear evidence linking the development of diabetes to defects in insulin secretion and action. However, our exciting new findings suggest that insulin-independent mechanisms, also referred to as “glucose effectiveness”, account for a major part of overall glucose disposal, and reduced glucose effectiveness also contributes to diabetes pathogenesis (Schwartz et al., Nature 2013). While the mechanisms underlying insulin-independent glucose disposal are poorly understood, our recent work suggests that the brain plays an important role as leptin action in the brain can normalize blood sugar levels in rodent models of type 1 diabetes. This antidiabetic effect of leptin involves a novel insulin-independent mechanism characterized by reduced rates of hepatic glucose production and increased rates of glucose uptake and establishes that the brain has the capacity to normalize blood glucose levels in uDM (German et al., Endocrinology 2011). Our overarching goal is to identify the neurocircuits in the brain that mediate this effect and understand how they communicate to peripheral tissues to control blood sugars.
To accomplish this, we utilize state-of-the-art neuroscience approaches, including both “optogenetics and DREADD” methodologies to selectively activate or inhibit specific neuronal populations in combination with genetic, molecular biological and immunohistochemical techniques. Our research effort is supported by a talented, dedicated research team and we collaborate with colleagues both within the University of Washington, including the laboratory of Michael Schwartz, and around the USA. Overall, our research identifies the brain as a possible new avenue for diabetes drug development.
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DOCE Researcher, Gregory Morton PhD, presents at American Diabetes Association’s 74th Scientific Sessions Symposium: The Brain in the Control of Glucose Homeostasis
- German JP, Thaler JP, Wisse BE, Shinsuke Oh-I, Sarruf DA, Fischer JD, Matsen ME, Taborsky Jr, GJ, Schwartz MW, Morton GJ. Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 2011 Feb; 152(2):394-404.
- Meek TH, Wisse BE, Thaler JP, Guyenet SJ, Matsen ME, Fischer JD, Taborsky Jr, GJ, Schwartz MW, Morton GJ. BDNF action in the brain attenuates diabetic hyperglycemia via insulin-independent inhibition of hepatic glucose production. Diabetes. 2013 May;62(5):1512-8. PMCID: PMC3636618.
- Meek TH, Matsen ME, Dorfman MD, Guyenet SJ, Damian V, Nguyen HT, Taborsky Jr, GJ, and Morton GJ. Leptin action in the ventromedial hypothalamic nucleus is sufficient, but not necessary, to normalize diabetic hyperglycemia. Endocrinology. 2013 Sep;154(9):3067-76.
- Schwartz MW, Seeley RJ, Tschop MH, Woods SC, Morton GJ, Myers MG, D’Alessio D. Cooperation between brain and islet in glucose homeostasis and diabetes. Nature. 2013 503:59-66.
- Morton GJ, Matsen ME, Bracy DP, Meek TH, Nguyen HT, Stefanovski D, Bergman RN, Wasserman DH, Schwartz MW. FGF19 action in the brain induces insulin-independent glucose lowering. J Clin Invest 2013 Nov 1;123(11):4799-4808.
- Morton GJ, Meek TH, Schwartz MW. Neurobiology of food intake in health and disease. Nat Rev Neurosci. 2014 15:367-378.
Members of the Laboratory
Diabetes and Obesity Center of Excellence
University of Washington School of Medicine
South Lake Union Campus
850 Republican Street Rm N334
Seattle, WA 98109-8055
Phone: (206) 897-5292
Lab: (206) 897-5280
To inquire about Postdoctoral and Graduate Student Openings click on: firstname.lastname@example.org