João Duarte, Diabetes and Brain Function
department of clinical sciences Lund
Ankita Talukdar, M Sc Student
Huseyin Erdogan, B Sc Student
Awatef Alhattami, Multipark student 2019
Natasha Molle, M Sc Student 2019
Adélaïde Alice Mohr, M Sc Student 2018
Andrea Castellani, Human Biology student 2018
Would you like to join our team?
Contact us (joao [dot] duarte [at] med [dot] lu [dot] se (Joao Duarte))
Diabetes has a major impact on brain function, but mechanisms of diabetic encephalopathy are not completely understood. Brain function requires continouos supply of glucose and ozygen, and a tight regulation of metabolic interactions between neurons and astrocytes. Loss of this metabolic regulation that fuels neuronal activity has been proposed to be the culprit of memory dysfunction, followed by an important neurodegenerative process.
Our research aims at understanding the molecular determinants underlying cognitive imparment associated to diabetes and metabolic syndrome components, including obesity, dyslipidemia, hypertension, insulin resistance or hyperglycemia. In particular, the lab´s major focus is on understanding astrocute-neuron metabolic interactions, how they are regulated to support adequate brain function, and how they adapt to metabolic disease states.
Our team has conducted several studies to understand the loss of neurometabolic coupling in insulin resistance. Using state-of-the-art 13C MRS in vivo, we have demonstrated for the first time a tight coupling between oxidative metabolism in astrocytic mitochondria and glutamatergic neurotransmission, defined by the rate of the glutamate-glutamine cycle (Glia 66(3): 477, 2018). However, in type 2 diabetes (T2D), insulin resistance is associated to impaired glucose utilization and glutamatergic transmission in neurons, while astrocytes display exacerbated metabolism and impaired glutamine and glycogen metabolism (Neurotox Res 36(2); 268, 2019: J Neurosci Res 97(8); 1004, 2019: Front Neurosci 12: 1015, 2019). This results point towards an important vulnerability of synaptic dysfunction within glutamatergic circuits, which is crucial for brain function and memory. In addition to investigating neurochemical mechanisms of disease, we investigate strategies for rescuing brain metabolic regulation and brain function in T2D.
We employ magnetic resonance methods to gain a better understanding of trajectories of diabetes-associated neurodegeneration, and of responses to therapeutic interventions. In particular, we detect metabolic markers of neurodegeneration by means of magnetic resonance spectroscopy (MRS). This method allows to address metabolic profiles in the native tissue with preserved cellular interactions, and might provide specific non-invasive biomarkers of diabetes-induced memory brain dysfunction.
Our current reserach is unveiling mechansims of insulin-dependent metabolic regulation in insulin resistance. In the long term, this knowledge will enable us to devise novel therapeutic strategies that directly target brain metabolic regulation for neuroprotection and improvement of brain function upon metabolic disease.
Wallenberg Center for Molecular Medicine
Swedish Research Council
Direktör Albert Påhlssons stifltelse
Royal Physiographic Society of Lund
Anna-Lisa Rosenberg Foundation
Stiftelsen Lars Hiertas Minne