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The iminosugar AMP-DNM improves satiety and activates brown adipose tissue through GLP1.
Diabetes 68, 2223-2234 (2019)
Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents. Moreover, we demonstrate that the mechanism mediating these favorable actions depends on oral, but not central, administration of AMP-DNM, which ultimately stimulates systemic glucagon-like peptide 1 (GLP1) secretion. We evidence an essential role of brain GLP1 receptors (GLP1r), as AMP-DNM fails to promote satiety and activate BAT in mice lacking the brain GLP1r as well as in mice treated intracerebroventricularly with GLP1r antagonist exendin-9. In conclusion, AMP-DNM markedly ameliorates metabolic abnormalities in obese rodents by restoring satiety and activating BAT through central GLP1r, while improving glucose homeostasis by mechanisms independent of central GLP1r.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Glucagon-like Peptide-1; Bitter Taste Receptor; Food-intake; Glucose-homeostasis; Insulin-resistance; Brain; Glycosphingolipids; Secretion; Agonist; Neurons
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Journal
Diabetes
Quellenangaben
Volume: 68,
Issue: 12,
Pages: 2223-2234
Publisher
American Diabetes Association
Publishing Place
Alexandria, VA.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)