Basic Study
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World J Diabetes. Sep 15, 2022; 13(9): 752-764
Published online Sep 15, 2022. doi: 10.4239/wjd.v13.i9.752
Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation
Christian Carpéné, Kristiyan Stiliyanov Atanasov, Francisco Les, Josep Mercader Barcelo
Christian Carpéné, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR 1297, Toulouse 31432, France
Kristiyan Stiliyanov Atanasov, Josep Mercader Barcelo, Molecular Biology and One Health research group, Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma 07122, Spain
Francisco Les, Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego, Zaragoza 50830, Spain
Author contributions: Carpéné C designed the studies, isolated cells for in vitro experiments, reviewed the literature, designed the figures, wrote and revised the manuscript; Mercader Barceló J performed animal treatments, non-invasive and ex vivo explorations, Stiliyanov Atanasov K was involved in data mining, Les F contributed to statistical analysis, literature review and revised the manuscript.
Institutional review board statement: The study was approved by the I2MC Institutional Review Board: Institut des maladies métaboliques et cadiovasculaires (http://www.i2mc.inserm.fr/accueil).
Institutional animal care and use committee statement: Mice were housed and manipulated according to the INSERM guidelines and European Directive 2010/63/UE by competent and expert technicians or researchers in animal care facilities with agreement number A 31 555 011. The experimental protocol was approved by the local ethical committee CREFRE.
Conflict-of-interest statement: The authors declare no competing financial interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guideline.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Christian Carpéné, PhD, Senior Researcher, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR 1297, Université Paul Sabatier Toulouse III, CHU Rangueil, Bat L4, BP 84225, Toulouse 31432, France. christian.carpene@inserm.fr
Received: March 11, 2022
Peer-review started: March 11, 2022
First decision: April 25, 2022
Revised: May 13, 2022
Accepted: August 22, 2022
Article in press: August 22, 2022
Published online: September 15, 2022
Processing time: 181 Days and 22.2 Hours
ARTICLE HIGHLIGHTS
Research background

Oral administration of benzylamine (Bza) exerts antihyperglycemic effects in obese and diabetic rodent models. This effect has been proposed to depend on the insulin-like action of Bza in adipose cells. The amine oxidation catalyzed by amine oxidases abundantly present in adipocytes generates hydrogen peroxide, which activates glucose transport.

Research motivation

To extrapolate the potential antihyperglycemic properties of Bza found in obese and diabetic models to the treatment of insulin-deficient type 1 diabetic states. Bza administration might facilitate glucose utilization to increase lipogenic and adipogenic activities in the adipose tissue and thereby improve glucose disposal even in the absence of insulin.

Research objectives

To evaluate the impact of Bza supplementation on hyperglycemia, polydipsia and hyperphagia in type 1 diabetic mouse, and to demonstrate that Bza metabolism by adipose tissue supports these antidiabetic effects.

Research methods

Bza solution (5 g/L, Bza-drinking) replaced drinking water in streptozotocin (STZ)-induced, insulin-deficient diabetic mice. Similar comparison between control and Bza-drinking groups was performed in normoglycemic mice. Nonfasting blood glucose, water and food intake were periodically recorded in the four groups. Adiposity was determined at the end of a 24-d treatment. Glucose transport in freshly isolated adipocytes was assessed ex vivo by determining the uptake of the nonmetabolizable radiolabeled 2-deoxyglucose.

Research results

Chronic Bza intake did not normalize hyperglycemia in STZ diabetic mice, despite it alleviating excessive water and food consumption. Bza intake had no effect on the limited body weight of the STZ diabetic mice and could not restore their dramatically reduced adipose tissue mass. In normoglycemic mice, the Bza-drinking group did not show altered body weight, or food or water consumption. However, when directly given in vitro to adipocytes isolated from nondiabetic mice, Bza was efficient in activating glucose uptake in both control and Bza-drinking groups.

Research conclusions

The capacity of Bza supplementation to reduce hyperglycemia, previously reported in obese and diabetic rodents, was not detectable in the emaciated and insulin-deficient STZ diabetic mice. However, the capacity of Bza to activate glucose transport in adipocytes was confirmed in nonobese, nondiabetic mice. It is likely that the adipose tissue atrophy induced by STZ challenge hampered the lipogenic and adipogenic action of Bza in this severe model of lipoatrophic, insulin-deficient diabetes.

Research perspectives

The current findings and their interpretations considerably limit the field of applications of oral Bza since this molecule did not work as an antidiabetic agent in rodents with reduced adiposity, as it is the case in type 1 STZ diabetic and lipoatrophic mice. Nevertheless, since SSAO substrates exhibit a direct action on glucose handling by fat cells, they still have potential interest for therapeutic use to combat other diabetic states.