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Diabetes and Brain Function

department of clinical sciences Lund
PI: João Duarte

Group members

João MN Duarte, PI

Alba M Garcia-Serrano, postdoc

Cecilia Skoug, PhD Student

João PP Vieira, PhD Student

Sara Larsson, research engineer

Ankita Talukdar, M Sc Student

Huseyin Erdogan, B Sc Student

Alumni

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))

Our research

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.

 

Brain_diabetes

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.

Brain_diabetes

Scientific impact

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.

Funding

Wallenberg Center for Molecular Medicine

STINT

Swedish Research Council

Diabetesfonden

Direktör Albert Påhlssons stifltelse

Crafoord Foundation

Royal Physiographic Society of Lund

Anna-Lisa Rosenberg Foundation

Stiftelsen Lars Hiertas Minne

 

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00