Carpéné C, Stiliyanov Atanasov K, Les F, Mercader Barcelo J. Hyperglycemia and reduced adiposity of streptozotocin-induced diabetic mice are not alleviated by oral benzylamine supplementation. World J Diabetes 2022; 13(9): 752-764 [PMID: 36188146 DOI: 10.4239/wjd.v13.i9.752]
Corresponding Author of This Article
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
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
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
Abstract
BACKGROUND
Benzylamine (Bza) oral administration delays the onset of hyperglycemia in insulin-resistant db-/- mice; a genetic model of obesity and type 2 diabetes.
AIM
To extend the antihyperglycemic properties of oral benzylamine to a model of insulin-deficient type 1 diabetes.
METHODS
Male Swiss mice were rendered diabetic by streptozotocin treatment (STZ) and divided in two groups: one received 0.5% Bza as drinking solution for 24 d (STZ Bza-drinking) while the other was drinking water ad libitum. Similar groups were constituted in age-matched, nondiabetic mice. Food intake, liquid intake, body weight gain and nonfasting blood glucose levels were followed during treatment. At the end of treatment, fasted glycemia, liver and white adipose tissue (WAT) mass were measured, while glucose uptake assays were performed in adipocytes.
RESULTS
STZ diabetic mice presented typical features of insulin-deficient diabetes: reduced body mass and increased blood glucose levels. These altered parameters were not normalized in the Bza-drinking group in spite of restored food and water intake. Bza consumption could not reverse the severe fat depot atrophy of STZ diabetic mice. In the nondiabetic mice, no difference was found between control and Bza-drinking mice for any parameter. In isolated adipocytes, hexose uptake was partially activated by 0.1 mmol/L Bza in a manner that was obliterated in vitro by the amine oxidase inhibitor phenelzine and that remained unchanged after Bza supplementation. Oxidation of 0.1 mmol/L Bza in WAT was lower in STZ diabetic than in normoglycemic mice.
CONCLUSION
Bza supplementation could not normalize the altered glucose handling of STZ diabetic mice with severe WAT atrophy. Consequently, its antidiabetic potential in obese and diabetic rodents does not apply to lipoatrophic type 1 diabetic mice.
Core Tip: In adipocytes, benzylamine (Bza) is oxidized by amine oxidases and stimulates glucose uptake. Bza oral administration alleviates insulin-resistant diabetes in obese and diabetic mice. It was investigated whether Bza was also antihyperglycemic in insulin-deficient type 1 diabetes. To this aim, a 0.5% Bza drinking solution was given to streptozotocin-induced diabetic mice. Oral Bza did not recover hyperglycemia and reduced adiposity of lipoatrophic and diabetic mice. A minimal level of adiposity was required to support benzylamine oxidation and to improve glucose utilization. Thus, the antidiabetic properties of Bza in obese and diabetic models, do not apply for diabetes with severe lipoatrophy.
