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      Evaluation of the Association Metformin: Plantago ovata Husk in Diabetic Rabbits

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          Abstract

          In this experimental study we have investigated whether the inclusion of the dietary fiber Plantago ovata husk could be recommended as coadjuvant in treatments with oral hypoglycemic drugs. We evaluated the use of Plantago ovata husk-metformin association in diabetic rabbits by determining its effects on glucose and insulin concentrations. Six groups of 6 rabbits were used. Groups 1 to 3 were fed with standard chow and groups 4 to 6 with chow supplemented with Plantago ovata husk (3.5 mg/kg/day). Two groups (numbers 1 and 4) were used as controls (receiving standard or supplemented chow), two groups (numbers 2 and 5) received metformin orally, and the other two (numbers 3 and 6) were treated orally with metformin and psyllium. Plasma glucose concentrations were lower in groups fed with fiber-supplemented chow whereas insulin levels showed important interindividual variations. Glucose pharmacokinetics parameters showed significant differences in C max and t max in relation to fiber intake. Insulin pharmacokinetics parameters after treatment with oral metformin showed an important increase in C max, AUC, and t max in animals fed with fiber. We conclude that Plantago ovata husk intake can contribute to the oral antihyperglycemic treatment of type 2 diabetes.

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          Metformin.

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            Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells.

            Metformin may benefit the macrovascular complications of diabetes independently of its conventional hypoglycemic effects. Accumulating evidence suggests that inflammatory processes participate in type 2 diabetes and its atherothrombotic manifestations. Therefore, this study examined the potential action of metformin as an inhibitor of pro-inflammatory responses in human vascular smooth muscle cells (SMCs), macrophages (Mphis), and endothelial cells (ECs). Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis. Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs. Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity. To address the significance of the anti-inflammatory effects of a therapeutically relevant plasma concentration of metformin (20 micromol/L), we conducted experiments in ECs treated with high glucose. Pretreatment with metformin also decreased phosphorylation of Akt and protein kinase C (PKC) in ECs under these conditions. These data suggest that metformin can exert a direct vascular anti-inflammatory effect by inhibiting NF-kappaB through blockade of the PI3K-Akt pathway. The novel anti-inflammatory actions of metformin may explain in part the apparent clinical reduction by metformin of cardiovascular events not fully attributable to its hypoglycemic action.
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              Role of AMP-activated protein kinase in mechanism of metformin action

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                Author and article information

                Journal
                J Diabetes Res
                J Diabetes Res
                JDR
                Journal of Diabetes Research
                Hindawi Publishing Corporation
                2314-6745
                2314-6753
                2015
                20 October 2015
                : 2015
                : 167526
                Affiliations
                Pharmacology, Institute of Biomedicine (IBIOMED), University of León, 24071 León, Spain
                Author notes
                *Raquel Díez-Láiz: rdielz@ 123456unileon.es

                Academic Editor: Aziz Ghahary

                Article
                10.1155/2015/167526
                4630395
                d6b15f2c-2daf-4ed4-a3c1-6bf18da35c0d
                Copyright © 2015 Raquel Díez-Láiz et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 November 2014
                : 15 January 2015
                Categories
                Research Article

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