IMINOSUGARS AND CORRECTION OF METABOLIC SYNDROME

 

Daniela Herrera Moro Chao 
d.herreramorochao@amc.uva.nl 

 

Supervisors: Hans Aerts & Andries Kalsbeek

Iminosugars, carbohydrate analogues with the ring oxygen replaced by nitrogen, have attracted interest from life science researchers for decades due to their remarkable chemical, biological and pharmaceutical properties. The action of natural iminosugars stems from their capacity to interfere with glycoconjugate processing activities and it is for this reason that iminosugars are widely regarded as ideal starting point for the development of new therapeutic agents. Some iminosugars are currently successfully applied to treat Gaucher disease and diabetes mellitus type 2.

The lypophilic iminosugar AMP-DMN or MZ21 (adamantine methyloxypentyl-deoxynojirimycin) has proven to be one of the most efficient molecules in correcting the hyperglycemia and the metabolic syndrome present in obesity and diabetes type 2 animal models, as compared to other iminosugar compounds. It is also the only compound capable of decreasing food intake and restoring satiety in obese animals. The present project aims to elucidate the mechanisms by which AMP-DMN exerts its behavioral and metabolic improvements. Our current hypothesis is that AMP-DMN will influence satiety and insulin sensitivity mainly by actions on the central nervous system.

Until now, our results indicate that the hypothalamus and brainstem are highly activated after administration of this drug. The activation of anorexigenic neuronal populations in both regions of the brain supports the idea that the central mechanisms are responsible for at least part of the metabolic improvements previously observed. 

 

         

A

 

B

 Activation of different neuronal populations after the administration of MZ21 and MZ31, 2 types of iminosugars.

A) aMSH activation in the area postrema after MZ21 treatment. B) NPY activation in the arcuate nucleus after MZ31 treatment.