Firas Younis

Tel Aviv University, Tell Afif, Tel Aviv, Israel

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Publications (6)21.31 Total impact

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    ABSTRACT: The objectives were to assess the potential of long-term prophylactic administration of telmisartan, an angiotensin II receptor antagonist and a partial peroxisome proliferator activator receptor (PPAR)γ agonist, in preventing the development of hypertension and hyperglycemia and to demonstrate the alteration in gene expression associated with the development of hyperglycemia and insulin resistance in Cohen-Rosenthal diabetic hypertensive rat, a unique model of hypertension and type 2 diabetes mellitus comorbidity. Cohen-Rosenthal diabetic hypertensive rats were continuously treated with telmisartan (3 mg/[kg d]) starting at age 6 to 8 weeks before developing hypertension or diabetes. Weight changes, blood pressure, blood insulin, adiponectin, glucose tolerance, and insulin sensitivity were monitored. Fat, liver, and muscle messenger RNAs were examined for the expression of genes potentially involved in the onset of insulin resistance. In addition to the expected antihypertensive effect of prophylactic telmisartan, diabetes was blunted, evidenced at the end of the study by a significantly lower glucose level. This was accompanied by improved glucose tolerance, increased sensitivity to insulin, reduction in fasting insulin levels and homeostasis model assessment index, as well as an increase in serum adiponectin. Telmisartan also prevented the increase in serum triglycerides and the associated appearance of lipid droplets in the liver. Diabetes induced tissue-specific changes in messenger RNAs expression of the following selected genes, which were restored by telmisartan treatment: PPARγ, PPARδ, PPARγ coactivator 1α, adiponectin, adiponectin receptor 1, adiponectin receptor 2, phosphotyrosine binding domain and a pleckstrin homology domain-containing adaptor protein, adenosine monophosphate kinase, and glucose translocator 4. Telmisartan blunted the development of hypertension, insulin resistance, and diabetes in prediabetic Cohen-Rosenthal diabetic hypertensive rats through pleiotropic activity, involving specific gene regulation of target organs.
    No preview · Article · Aug 2011 · Metabolism: clinical and experimental
  • F. Younis · Y. Oron · N. Stern · R. Limor · T. Rosenthal

    No preview · Article · Jun 2011 · Journal of Hypertension
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    ABSTRACT: The importance of hypertension treatment has expanded beyond blood pressure management to include additional risk factors, mainly diabetes. It was considered of interest to test the effect of telmisartan, an angiotensin receptor 1 antagonist and peroxisome proliferator activator receptor-gamma partial agonist, on Cohen-Rosenthal diabetic hypertensive nonobese (CRDH) rats, a unique model combining both pathologies. Its effect was examined on fat-derived and inflammatory agents in CRDH. To determine the extent of the drug's peroxisome proliferator activator receptor-gamma modulating beneficial metabolic actions, results were compared with those obtained with valsartan and rosiglitazone in CRDH and Cohen diabetic rat (CDR). Telmisartan and valsartan were given in drinking water at 3 and 12 mg/kg/d, whereas rosiglitazone (3 mg/kg/d) was given as food admixture for a period of 5 months. Blood pressure, glucose, insulin, adiponectin, leptin, and tumor necrosis factor alpha were examined. Telmisartan and valsartan significantly (P < .01) reduced blood pressure, whereas telmisartan and rosiglitazone considerably reduced blood glucose levels to normoglycemic levels (P < .01) in these 2 strains. Insulin levels were not affected by telmisartan and valsartan but were slightly reduced by rosiglitazone in CDR. In contrast to valsartan, adiponectin was significantly (60%, P < .01) increased by telmisartan in both CDR and CRDH, whereas rosiglitazone induced a 60% and 180% increase in CRDH and CDR animals, respectively, on day 30 of treatment. Co-treatment with GW9662 averted telmisartan-induced rise of adiponectin. Tumor necrosis factor alpha declined in telmisartan-treated rats, less so with rosiglitazone, but not valsartan. Telmisartan also induced downsizing of epididymal adipocytes compared with valsartan. Leptin levels were significantly increased by valsartan (P < .05) but reduced by telmisartan and rosiglitazone. The telmisartan-induced increase in adiponectin was most probably associated with a decrease in glucose and tumor necrosis factor alpha levels. Therefore, in addition to its hypotensive effect, telmisartan demonstrated beneficial thiazolidinedione-like effects.
    No preview · Article · Aug 2010 · Metabolism: clinical and experimental
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    ABSTRACT: J Clin Hypertens (Greenwich). 2010;12:451–455. ©2010 Wiley Periodicals, Inc. S-allyl-mercapto-captopril (CPSSA) is a conjugate of captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic syndrome abnormalities, including weight preservation, observed by the authors in fructose-induced hypertensive hyperinsulinemic rats and in Koletsky rats. The aim of the study was to examine blood pressure (BP) and glucose levels in the Cohen-Rosenthal Diabetic Hypertensive (CRDH) model as well as to follow their weight preservation. CRDH rats (n=14) were fed the sugar-rich copper-free diet essential for the development of diabetes mellitus. Two months later BP and blood glucose levels were measured. CPSSA was diluted in drinking water and administered at a final dose of 53.5 mg/kg/d (n=8). Control rats (n=6) received no drug (vehicle group). In contrast to control group, CPSSA prevented progressive weight gain, without a detectable effect on food and water intake. CPSSA was effective in attenuating systolic and diastolic BP (P<0.01) as well as significantly reducing glucose levels (P<0.01). Control rats continued to gain weight, whereas the groups fed CPSSA did not. CPSSA was shown to have additional beneficial effects on improving BP and glucose level, as well as preserving weight gain. The authors conclude that the combined molecule CPSSA integrates the antihypertensive feature of both allicin and captopril, making it a potential antidiabetic and cardiovascular protective agent.
    Preview · Article · Jun 2010 · Journal of Clinical Hypertension
  • F Younis · Y Oron · R Limor · N Stern · T Rosenthal

    No preview · Article · Jun 2010 · Journal of Hypertension
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    ABSTRACT: The antihypertensive and hypoglycemic effects of telmisartan, which has dual angiotensin II antagonist-PPAR-gamma agonist properties, was studied in Cohen-Rosenthal Diabetic Hypertensive rats (CRDH), a model in which hypertension, insulin resistance, and diabetes co-exist. CRDH, Cohen-diabetic rats (CDR), and SHR received telmisartan (3 mg/kg/day in drinking water) for five months. Telmisartan significantly lowered systolic and diastolic BP in SHR and CRDH, independent of body weight, and remained fairly constant in controls throughout the experiment. Blood glucose levels fell rapidly in the treated animals and remained steady in controls. Results indicate that telmisartan is a prototype of a new approach to treating coexisting diabetes and hypertension.
    No preview · Article · Sep 2007 · Clinical and Experimental Hypertension