Metabolism-independent sugar sensing in central orexin neurons.
OBJECTIVE: Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocre...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2008
|
| _version_ | 1826264209989566464 |
|---|---|
| author | González, J Jensen, LT Fugger, L Burdakov, D |
| author_facet | González, J Jensen, LT Fugger, L Burdakov, D |
| author_sort | González, J |
| collection | OXFORD |
| description | OBJECTIVE: Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells. RESEARCH DESIGN AND METHODS: We carried out patch-clamp recordings of the electrical activity of individual orexin neurons unambiguously identified by transgenic expression of green fluorescent protein in mouse brain slices. RESULTS- We show that 1) 2-deoxyglucose, a nonmetabolizable glucose analog, mimics the effects of glucose; 2) increasing intracellular energy fuel production with lactate does not reproduce glucose responses; 3) orexin cell glucose sensing is unaffected by glucokinase inhibitors alloxan, d-glucosamine, and N-acetyl-d-glucosamine; and 4) orexin glucosensors detect mannose, d-glucose, and 2-deoxyglucose but not galactose, l-glucose, alpha-methyl-d-glucoside, or fructose. CONCLUSIONS: Our new data suggest that behaviorally critical neurocircuits of the lateral hypothalamus contain glucose detectors that exhibit novel sugar selectivity and can operate independently of glucose metabolism. |
| first_indexed | 2024-03-06T20:04:06Z |
| format | Journal article |
| id | oxford-uuid:2854f7e2-01dc-457c-8d8f-ad9a721726cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:04:06Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:2854f7e2-01dc-457c-8d8f-ad9a721726cf2022-03-26T12:12:17ZMetabolism-independent sugar sensing in central orexin neurons.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2854f7e2-01dc-457c-8d8f-ad9a721726cfEnglishSymplectic Elements at Oxford2008González, JJensen, LTFugger, LBurdakov, D OBJECTIVE: Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells. RESEARCH DESIGN AND METHODS: We carried out patch-clamp recordings of the electrical activity of individual orexin neurons unambiguously identified by transgenic expression of green fluorescent protein in mouse brain slices. RESULTS- We show that 1) 2-deoxyglucose, a nonmetabolizable glucose analog, mimics the effects of glucose; 2) increasing intracellular energy fuel production with lactate does not reproduce glucose responses; 3) orexin cell glucose sensing is unaffected by glucokinase inhibitors alloxan, d-glucosamine, and N-acetyl-d-glucosamine; and 4) orexin glucosensors detect mannose, d-glucose, and 2-deoxyglucose but not galactose, l-glucose, alpha-methyl-d-glucoside, or fructose. CONCLUSIONS: Our new data suggest that behaviorally critical neurocircuits of the lateral hypothalamus contain glucose detectors that exhibit novel sugar selectivity and can operate independently of glucose metabolism. |
| spellingShingle | González, J Jensen, LT Fugger, L Burdakov, D Metabolism-independent sugar sensing in central orexin neurons. |
| title | Metabolism-independent sugar sensing in central orexin neurons. |
| title_full | Metabolism-independent sugar sensing in central orexin neurons. |
| title_fullStr | Metabolism-independent sugar sensing in central orexin neurons. |
| title_full_unstemmed | Metabolism-independent sugar sensing in central orexin neurons. |
| title_short | Metabolism-independent sugar sensing in central orexin neurons. |
| title_sort | metabolism independent sugar sensing in central orexin neurons |
| work_keys_str_mv | AT gonzalezj metabolismindependentsugarsensingincentralorexinneurons AT jensenlt metabolismindependentsugarsensingincentralorexinneurons AT fuggerl metabolismindependentsugarsensingincentralorexinneurons AT burdakovd metabolismindependentsugarsensingincentralorexinneurons |