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      Differential effect of metformin and/or glyburide on apelin serum levels in patients with type 2 diabetes mellitus: Concepts and clinical practice

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          Abstract

          Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with abundant adipocytokine changes which may play an important role in the progression of insulin resistance and micro- and macro-vascular complications. Therefore, the objective of this study was to assess the differential effect of metformin alone or in combination with glyburide on apelin serum levels in patients with T2DM. In this case–control study, fifty patients with T2DM in the age range of 45–65 years and twenty-five healthy controls matched for age and body weight were recruited from single endocrinology center, subdivided according to the diabetic pharmacotherapy into: Group I: healthy controls ( n = 25), Group II: T2DM patients on metformin ( n = 15), Group III: T2DM patients on glyburide ( n = 17), and Group IV: T2DM patients on metformin plus glyburide ( n = 28). Biochemical and anthropometric variables in relation to apelin serum levels were estimated. Apelin serum levels were low in normal healthy controls compared to T2DM patients ( P < 0.01). The differential effect of diabetic pharmacotherapy on apelin serum level was statistically significant ( P < 0.01) compared to the controls, but insignificant when compared among used drugs ( P > 0.05). Apelin level was high in T2DM compared to the controls; both metformin and glyburide might play a role in this elevation.

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          Apelin is necessary for the maintenance of insulin sensitivity.

          The recently discovered peptide apelin is known to be involved in the maintenance of insulin sensitivity. However, questions persist regarding its precise role in the chronic setting. Fasting glucose, insulin, and adiponectin levels were determined on mice with generalized deficiency of apelin (APKO). Additionally, insulin (ITT) and glucose tolerance tests (GTT) were performed. To assess the impact of exogenously delivered apelin on insulin sensitivity, osmotic pumps containing pyroglutamated apelin-13 or saline were implanted in APKO mice for 4 wk. Following the infusion, ITT/GTTs were repeated and the animals euthanized. Soleus muscles were harvested and homogenized in lysis buffer, and insulin-induced Akt phosphorylation was determined by Western blotting. Apelin-13 infusion and ITTs/GTTs were also performed in obese diabetic db/db mice. To probe the underlying mechanism for apelin's effects, apelin-13 was also delivered to cultured C2C12 myotubes. 2-[3H]deoxyglucose uptake and Akt phosphorylation were assessed in the presence of various inhibitors. APKO mice had diminished insulin sensitivity, were hyperinsulinemic, and had decreased adiponectin levels. Soleus lysates had decreased insulin-induced Akt phosphorylation. Administration of apelin to APKO and db/db mice resulted in improved insulin sensitivity. In C2C12 myotubes, apelin increased glucose uptake and Akt phosphorylation. These events were fully abrogated by pertussis toxin, compound C, and siRNA knockdown of AMPKalpha1 but only partially diminished by LY-294002 and not at all by L-NAME. We conclude that apelin is necessary for the maintenance of insulin sensitivity in vivo. Apelin's effects on glucose uptake and Akt phosphorylation are in part mediated by a G(i) and AMPK-dependent pathway.
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            Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes

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              Apelin Treatment Increases Complete Fatty Acid Oxidation, Mitochondrial Oxidative Capacity, and Biogenesis in Muscle of Insulin-Resistant Mice

              Both acute and chronic apelin treatment have been shown to improve insulin sensitivity in mice. However, the effects of apelin on fatty acid oxidation (FAO) during obesity-related insulin resistance have not yet been addressed. Thus, the aim of the current study was to determine the impact of chronic treatment on lipid use, especially in skeletal muscles. High-fat diet (HFD)-induced obese and insulin-resistant mice treated by an apelin injection (0.1 μmol/kg/day i.p.) during 4 weeks had decreased fat mass, glycemia, and plasma levels of triglycerides and were protected from hyperinsulinemia compared with HFD PBS-treated mice. Indirect calorimetry experiments showed that apelin-treated mice had a better use of lipids. The complete FAO, the oxidative capacity, and mitochondrial biogenesis were increased in soleus of apelin-treated mice. The action of apelin was AMP-activated protein kinase (AMPK) dependent since all the effects studied were abrogated in HFD apelin-treated mice with muscle-specific inactive AMPK. Finally, the apelin-stimulated improvement of oxidative capacity led to decreased levels of acylcarnitines and enhanced insulin-stimulated glucose uptake in soleus. Thus, by promoting complete lipid use in muscle of insulin-resistant mice through mitochondrial biogenesis and tighter matching between FAO and the tricarboxylic acid cycle, apelin treatment could contribute to insulin sensitivity improvement.
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                Author and article information

                Journal
                J Adv Pharm Technol Res
                J Adv Pharm Technol Res
                JAPTR
                Journal of Advanced Pharmaceutical Technology & Research
                Medknow Publications & Media Pvt Ltd (India )
                2231-4040
                0976-2094
                Jul-Sep 2018
                : 9
                : 3
                : 80-86
                Affiliations
                [1]Department of Pharmacology, Toxicology and Medicine, College of Medicine, Almustansiriya University, Baghdad, Iraq
                Author notes
                Address for correspondence: Dr. Hayder M. Al-Kuraishy, Department of Pharmacology, Toxicology and Medicine, College of Medicine, Almustansiriya University, P.O. Box. 14132, Baghdad, Iraq. E-mail: hayderm36@ 123456yahoo.com
                Article
                JAPTR-9-80
                10.4103/japtr.JAPTR_273_18
                6174705
                30338233
                e8e2e313-fa7f-47fa-b796-7ea4c165806c
                Copyright: © 2018 Journal of Advanced Pharmaceutical Technology & Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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                Original Article

                Pharmacology & Pharmaceutical medicine
                apelin,glyburide,metformin,type 2 diabetes mellitus
                Pharmacology & Pharmaceutical medicine
                apelin, glyburide, metformin, type 2 diabetes mellitus

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