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Apelin targets gut contraction to control glucose metabolism via the brain.
- Source :
-
Gut [Gut] 2017 Feb; Vol. 66 (2), pp. 258-269. Date of Electronic Publication: 2015 Nov 12. - Publication Year :
- 2017
-
Abstract
- Objective: The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus.<br />Design: We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose.<br />Results: In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle.<br />Conclusions: Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders.<br />Competing Interests: Conflicts of Interest: None declared.<br /> (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Subjects :
- Animals
Apelin
Biosensing Techniques
Diabetes Mellitus physiopathology
Duodenum drug effects
Duodenum metabolism
Enteric Nervous System physiology
Gastrointestinal Motility drug effects
Homeostasis
Hypothalamus metabolism
Male
Mice
Mice, Inbred C57BL
Muscle, Smooth physiology
Nitric Oxide metabolism
Obesity physiopathology
Telemetry
Adipokines pharmacology
Enteric Nervous System drug effects
Glucose metabolism
Hypothalamus drug effects
Intercellular Signaling Peptides and Proteins pharmacology
Muscle Contraction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3288
- Volume :
- 66
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 26565000
- Full Text :
- https://doi.org/10.1136/gutjnl-2015-310230