Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes
Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglycaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metab...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3422 |
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| author | Paul G. Weightman Potter Kate L. J. Ellacott Andrew D. Randall Craig Beall |
| author_facet | Paul G. Weightman Potter Kate L. J. Ellacott Andrew D. Randall Craig Beall |
| author_sort | Paul G. Weightman Potter |
| collection | DOAJ |
| description | Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglycaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose (LG) treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca<sup>2+</sup> levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca<sup>2+</sup> responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that prevents RLG-induced mitochondrial adaptations. |
| first_indexed | 2024-03-09T19:11:08Z |
| format | Article |
| id | doaj.art-29126711bddc4d2ab8c82c6d26c8075c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:08Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-29126711bddc4d2ab8c82c6d26c8075c2023-11-24T04:08:33ZengMDPI AGCells2073-44092022-10-011121342210.3390/cells11213422Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat AstrocytesPaul G. Weightman Potter0Kate L. J. Ellacott1Andrew D. Randall2Craig Beall3Department of Clinical and Biomedical Sciences, Faculty of Medicine and Health, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UKDepartment of Clinical and Biomedical Sciences, Faculty of Medicine and Health, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UKDepartment of Clinical and Biomedical Sciences, Faculty of Medicine and Health, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UKDepartment of Clinical and Biomedical Sciences, Faculty of Medicine and Health, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UKAstrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglycaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose (LG) treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca<sup>2+</sup> levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca<sup>2+</sup> responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that prevents RLG-induced mitochondrial adaptations.https://www.mdpi.com/2073-4409/11/21/3422astrocyteshypoglycemiadiabetes mellitustype 1mitochondriaglycemic control |
| spellingShingle | Paul G. Weightman Potter Kate L. J. Ellacott Andrew D. Randall Craig Beall Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes Cells astrocytes hypoglycemia diabetes mellitus type 1 mitochondria glycemic control |
| title | Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes |
| title_full | Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes |
| title_fullStr | Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes |
| title_full_unstemmed | Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes |
| title_short | Glutamate Prevents Altered Mitochondrial Function Following Recurrent Low Glucose in Hypothalamic but Not Cortical Primary Rat Astrocytes |
| title_sort | glutamate prevents altered mitochondrial function following recurrent low glucose in hypothalamic but not cortical primary rat astrocytes |
| topic | astrocytes hypoglycemia diabetes mellitus type 1 mitochondria glycemic control |
| url | https://www.mdpi.com/2073-4409/11/21/3422 |
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