IBRI DIABETES CENTER (IDC) - FLAK LAB
Focus: The CNS control of individual aspects of energy balance and glucose homeostasis.
It is well understood that the brain can control energy balance via descending connections (i.e. sympathetic nervous system) with peripheral organs (e.g. pancreas, heart, liver, adrenal). However, the details of these brain systems have not yet been established. While therapies exist that can successfully target the sympathetic nervous system to restore normal function in obese and diabetic patients, these tools also produce deleterious effects on unwanted and unrelated processes (e.g. cardiovascular disease, renal failure). Thus, the upstream neural system that can specifically target, for example, glucose mobilization, represents the ideal target to curb medical issues associated with complications such as hypoglycemia. Yet, there is only a superficial understanding, at this time, of the unique cellular components (e.g. neurotransmitters, receptors, and/or transcription factors) contained within the neural circuits that control these processes.
Dr. Jonathan Flak, who joined the IBRI in the fall of 2019, and his team, are investigating how the brain can separately initiate the glucose mobilization and glucose uptake, with the help of the ADA Pathway Program. Dr. Flak’s goal is to identify ways to target these circuits to promote glucose mobilization during hypoglycemia or curb diabetic hyperglycemia.
In addition to the control of glucose, many overlapping components in the brain that influence glucose homeostasis also can influence energy expenditure. Concurrently, the Flak Lab also aims to understand the circuits in the brain that separately control energy expenditure, especially those circuits that can be promoted during periods of exercise.
Using mouse models, the Flak Lab is working to identify the neural circuits, as well as the essential components (e.g. receptors, transmitters, transcription factors) within these circuits, that are responsible for generating these responses. These studies may reveal new targets for the treatment of obesity and diabetes.
Within the last few years, Dr. Flak has revealed brainstemàhypothalamus circuits that can mobilize blood glucose during periods of hypoglycemia and pain/inflammation, leading to publications in Nature Neuroscience and the Journal of Clinical Investigation. Dr. Flak is working to establish the downstream connections from the hypothalamus to understand how these signals communicate with the peripheral organs in order to generate the mobilization of blood glucose, glucose uptake and facilitate energy expenditure.