FP33-4 Neurogliaform interneurons represent local sources of insulin in the cerebral cortex

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP33-Insulin Signaling & Inflammation
Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 303 (Moscone Center)

Poster Board MON-846
Gabor Tamas*1, Gabor Molnar1, Nora Farago2, Agnes K Kocsis1, Marton Rozsa1, Sandor Lovas1, Eszter Boldog1, Rita Baldi1, Janos Gardi1, Laszlo G Puskas2 and Eva Csajbok1
1University of Szeged, Hungary, 2Biological Research Center, Hungarian Academy of Sciences, Hungary
Concentrations of insulin in the brain are ten to hundred times higher compared to blood plasma levels. Insulin in the brain regulates the metabolism, molecular composition and cognitive performance of microcircuits, reduces food intake and cerebral insulin levels are altered in diabetes, aging, obesity and Alzheimer’s disease. Released by pancreatic beta cells, insulin passes the blood brain barrier by a saturable transport mechanism, but local sources of cerebral insulin still remain unclear.

Using whole-cell patch clamp recordings followed by single cell PCR, we find that insulin mRNA is strongly expressed in an identified subset of GABAergic interneurons in the cerebral cortex of the rat. These results were confirmed by immunocytochemistry detecting insulin in a subpopulation of GABAergic cells. Insulin mRNA copy numbers vary according to extracellular glucose concentrations as detected by single cell digital PCR in interneurons which were characterized electrophysiologically and reconstructed anatomically. In addition, gene chip analysis performed on these identified GABAergic cells comparing hyper- and hypoglycemic conditions suggests changes in the expression of several genes functionally linked to insulin. Moreover, our experiments show that insulin release enhancing compounds promote de novo insulin synthesis in brain slices as detected by radioimmunoassay. Furthermore, targeted electrophysiological application of the same compounds to interneurons expressing insulin mimics the effect of external insulin on local microcircuits via insulin receptors.

These results identify a subset of neocortical GABAergic interneurons as sources of insulin in the central nervous system and propose a link between GABAergic and insulin mediated action in cortical microcircuits.

Nothing to Disclose: GT, GM, NF, AKK, MR, SL, EB, RB, JG, LGP, EC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by the ERC, EURYI, NIH N535915, Hungarian Academy of Sciences (G.T.) and the Bolyai Fellowship (G.M.).