BBB Seminar: Bryndis Birnir
Insulin and GABA as mediators in cross-talks between the metabolic and the nervous systems
Bryndis Birnir, Department of Neuroscience, Uppsala University, Sweden
Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. Gamma-aminobutyric acid (GABA) decreases neuronal excitability by activating GABAA channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. We have shown in acute rat hippocamal slices that insulin (1 nM) “turns on” new extrasynaptic GABAA channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. GABA is also an extracellular signal molecule in the pancreatic islets. GABA is produced in the insulin producing beta cells where it is present both in the cytoplasm and in vesicles. Once released, GABA is thought to act in an auto- and paracrine manner on the islet cells to modulate hormone secretion. The effective interstitial physiological concentration of GABA in islets is not known. Keeping the proper levels may be critical for balancing insulin and glucagon secretion. I will discuss data from human islets that demonstrate that the expression of GABAA channel subunits is modified in islets from individuals with type 2 diabetes. Hormone secretion is altered in these islets but can be modified with GABAA and GABAB drugs.
Host: Margaret Lin Veruki, Department of Biomedicine