The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1 | Zendy

Daniela Herrera Moro Chao | Zendy; Yanan Wang | Zendy; Ewout Foppen | Zendy; Roelof Ottenhoff | Zendy; Cindy van Roomen | Zendy; Edwin T. Parlevliet | Zendy; Marco van Eijk | Zendy; Marri Verhoek | Zendy; Rolf G. Boot | Zendy; André R. A. Marques | Zendy; Saskia Scheij | Zendy; Mina Mirzaian | Zendy; Sander Kooijman | Zendy; Kirstin Jansen | Zendy; Dawei Wang | Zendy; Clarita Mergen | Zendy; Randy J. Seeley | Zendy; Matthias H. Tschöp | Zendy; Herman S. Overkleeft | Zendy; Patrick C.N. Rensen | Zendy; Andries Kalsbeek | Zendy; Johannes M. F. G. Aerts | Zendy; ChunXia Yi | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1

Author(s) -

Daniela Herrera Moro Chao,

Yanan Wang,

Ewout Foppen,

Roelof Ottenhoff,

Cindy van Roomen,

Edwin T. Parlevliet,

Marco van Eijk,

Marri Verhoek,

Rolf G. Boot,

André R. A. Marques,

Saskia Scheij,

Mina Mirzaian,

Sander Kooijman,

Kirstin Jansen,

Dawei Wang,

Clarita Mergen,

Randy J. Seeley,

Matthias H. Tschöp,

Herman S. Overkleeft,

Patrick C.N. Rensen,

Andries Kalsbeek,

Johannes M. F. G. Aerts,

ChunXia Yi

Publication year - 2019

Publication title -

diabetes

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.219

H-Index - 330

eISSN - 1939-327X

pISSN - 0012-1797

DOI - 10.2337/db19-0049

Subject(s) - medicine , endocrinology , brown adipose tissue , glucose homeostasis , adipose tissue , glucagon like peptide 1 , receptor , antagonist , homeostasis , type 2 diabetes , chemistry , biology , obesity , diabetes mellitus , insulin resistance

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research