Hypothalamic Mechanisms Mediating Sustained Glucose-Lowering by FGF1 Action in the Brain

Current treatment regimens for type 2 diabetes (T2D) can delay disease progression, but they do not achieve lasting diabetes remission and hence cannot prevent disease progression. Therefore, a compelling need for new, more effective treatment options exists, and growing evidence points to brain neurocircuits involved in glucose homeostasis as potential therapeutic targets. Support for the translational potential of targeting brain glucoregulatory circuits is highlighted by studies demonstrating that deep brain stimulation can improve glycemic control in humans with T2D. However, to fully realize the potential of such translational advances, an improved understanding of the central mechanisms that control glucose homeostasis is required. The overarching goal of this proposal is to use Fibroblast Growth Factor 1 as a pharmacological tool with which to advance our understanding of how glucose homeostasis is controlled by the brain and thereby to inform the development of novel therapeutics for patients with T2D.