English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/172914
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Differential effects of metformin glycinate and hydrochloride in glucose production, AMPK phosphorylation and insulin sensitivity in hepatocytes from non-diabetic and diabetic mice

AuthorsRada, Patricia; Mosquera, Alejandra; Muntané, Jordi; Ferrandiz, Francisco; Rodriguez-Mañas, Leocadio; Pablo, Flora de ; González-Canudas, Jorge; Valverde, Ángela M.
KeywordsDiabetes
Metformin
Insulin resistance
Glucose homeostasis
Liver
Issue Date2019
PublisherElsevier
CitationFood and Chemical Toxicology 123: 470-480 (2019)
AbstractThe liver is a main target tissue of the biguanide metformin which activates AMP-activated protein kinase (AMPK). We previously reported that administration of metformin glycinate showed a greater decrease of glycated hemoglobin A1c than a placebo in patients with type 2 diabetes mellitus (T2DM). In this study, we compared the effects of metformin hydrochloride, the oral antidiabetic drug of first choice, with those of metformin glycinate in hepatocytes from non-diabetic and diabetic mice and humans. Both formulations were equally potent regard to the reduction of basal and glucagon-induced glucose production and mRNA levels of gluconeogenic enzymes (Pck1 and G6pc) in hepatocytes from C57/Bl6 mice and humans. On the contrary, phosphorylation of AMPK and its substrate acetyl CoA carboxylase (ACC) was faster in hepatocytes treated with metformin glycinate. Likewise, we found stronger reduction in hepatocytes from obese/diabetic db/db mice of glucagon-induced glucose output and more sustained AMPK phosphorylation after treatment with metformin glycinate. Importantly, insulin sensitization regarding phosphorylation of AKT (Ser473) was enhanced in hepatocytes from db/db mice or humans pretreated with metformin glycinate. In conclusion, our data indicate that metformin glycinate may be an alternative therapy against insulin resistance during obesity and/or T2DM.
Publisher version (URL)https://doi.org/10.1016/j.fct.2018.11.019
URIhttp://hdl.handle.net/10261/172914
DOI10.1016/j.fct.2018.11.019
ISSN0278-6915
E-ISSN1873-6351
Appears in Collections:(IIBM) Artículos
(CIB) Artículos
(IBIS) Artículos
Files in This Item:
File Description SizeFormat 
RadaFCT-D-18-01715R1.pdf2,93 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.