Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition.

Autor: Karavia EA; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Hatziri A; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Kalogeropoulou C; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Papachristou NI; Anatomy, Histology and Embryology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Xepapadaki E; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Constantinou C; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Natsos A; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Petropoulou PI; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Sasson S; Institute for Drug Research, Department of Pharmacology, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel., Papachristou DJ; Anatomy, Histology and Embryology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece., Kypreos KE; Pharmacology Department, University of Patras Medical School, Rio, Achaias TK 26500, Greece. Electronic address: kkypreos@med.upatras.gr.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2015 Nov 05; Vol. 766, pp. 76-85. Date of Electronic Publication: 2015 Sep 28.
DOI: 10.1016/j.ejphar.2015.09.040
Abstrakt: Recently, we showed that deficiency in apolipoprotein A-I (ApoA-I) sensitizes mice to diet-induced obesity, glucose intolerance and NAFLD. Here we investigated the potential involvement of ApoA-I in the pharmacological effects of metformin on glucose intolerance and NAFLD development. Groups of apoa1-deficient (apoa1(-/-)) and C57BL/6 mice fed western-type diet were either treated with a daily dose of 300 mg/kg metformin for 18 weeks or left untreated for the same period. Then, histological and biochemical analyses were performed. Metformin treatment led to a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-) mice following intraperitoneal glucose tolerance test. However, only metformin-treated C57BL/6 mice maintained sufficient peripheral insulin sensitivity to effectively clear glucose following the challenge, as indicated by a [(3)H]-2-deoxy-D-glucose uptake assay in isolated soleus muscle. Similarly, deficiency in ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD development. Gene expression analysis indicated that the effects of ApoA-I on metformin treatment may be independent of adenosine monophosphate-activated protein kinase (AMPK) activation and de novo lipogenesis. Interestingly, metformin treatment reduced mitochondrial oxidative phosphorylation function only in apoa1(-/-) mice. Our data show that the role of ApoA-I in diabetes extends to the modulation of the pharmacological actions of metformin, a common drug for the treatment of type 2 diabetes.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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