RT Journal Article
T1 Differential effects of metformin glycinate and hydrochloride in glucose production, AMPK phosphorylation and insulin sensitivity in hepatocytes from non-diabetic and diabetic mice.
A1 Rada, Patricia
A1 Mosquera, Alejandra
A1 Muntané, Jordi
A1 Ferrandiz, Francisco
A1 Rodriguez-Mañas, Leocadio
A1 de Pablo, Flora
A1 González-Canudas, Jorge
A1 Valverde, Ángela M
K1 Diabetes
K1 Glucose homeostasis
K1 Insulin resistance
K1 Liver
K1 Metformin
AB The 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.
YR 2018
FD 2018-11-09
LK http://hdl.handle.net/10668/13167
UL http://hdl.handle.net/10668/13167
LA en
DS RISalud
RD Apr 14, 2025