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12.01.2019 | Article

Expression of GLP-1 receptors in insulin-containing interneurons of rat cerebral cortex

verfasst von: Éva A. Csajbók, Ágnes K. Kocsis, Nóra Faragó, Szabina Furdan, Balázs Kovács, Sándor Lovas, Gábor Molnár, István Likó, Ágnes Zvara, László G. Puskás, Attila Patócs, Gábor Tamás

Erschienen in: Diabetologia | Ausgabe 4/2019

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Abstract

Aims/hypothesis

Glucagon-like peptide 1 (GLP-1) receptors are expressed by pancreatic beta cells and GLP-1 receptor signalling promotes insulin secretion. GLP-1 receptor agonists have neural effects and are therapeutically promising for mild cognitive impairment and Alzheimer’s disease. Our previous results showed that insulin is released by neurogliaform neurons in the cerebral cortex, but the expression of GLP-1 receptors on insulin-producing neocortical neurons has not been tested. In this study, we aimed to determine whether GLP-1 receptors are present in insulin-containing neurons.

Methods

We harvested the cytoplasm of electrophysiologically and anatomically identified neurogliaform interneurons during patch-clamp recordings performed in slices of rat neocortex. Using single-cell digital PCR, we determined copy numbers of Glp1r mRNA and other key genes in neurogliaform cells harvested in conditions corresponding to hypoglycaemia (0.5 mmol/l glucose) and hyperglycaemia (10 mmol/l glucose). In addition, we performed whole-cell patch-clamp recordings on neurogliaform cells to test the effects of GLP-1 receptor agonists for functional validation of single-cell digital PCR results.

Results

Single-cell digital PCR revealed GLP-1 receptor expression in neurogliaform cells and showed that copy numbers of mRNA of the Glp1r gene in hyperglycaemia exceeded those in hypoglycaemia by 9.6 times (p < 0.008). Moreover, single-cell digital PCR confirmed co-expression of Glp1r and Ins2 mRNA in neurogliaform cells. Functional expression of GLP-1 receptors was confirmed with whole-cell patch-clamp electrophysiology, showing a reversible effect of GLP-1 on neurogliaform cells. This effect was prevented by pre-treatment with the GLP-1 receptor-specific antagonist exendin-3(9-39) and was absent in hypoglycaemia. In addition, single-cell digital PCR of neurogliaform cells revealed that the expression of transcription factors (Pdx1, Isl1, Mafb) are important in beta cell development.

Conclusions/interpretation

Our results provide evidence for the functional expression of GLP-1 receptors in neurons known to release insulin in the cerebral cortex. Hyperglycaemia increases the expression of GLP-1 receptors in neurogliaform cells, suggesting that endogenous incretins and therapeutic GLP-1 receptor agonists might have effects on these neurons, similar to those in pancreatic beta cells.

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Titel: Expression of GLP-1 receptors in insulin-containing interneurons of rat cerebral cortex
verfasst von: Éva A. Csajbók
Ágnes K. Kocsis
Nóra Faragó
Szabina Furdan
Balázs Kovács
Sándor Lovas
Gábor Molnár
István Likó
Ágnes Zvara
László G. Puskás
Attila Patócs
Gábor Tamás
Publikationsdatum: 12.01.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 4/2019
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4803-z

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Expression of GLP-1 receptors in insulin-containing interneurons of rat cerebral cortex

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