Effect of antihypertensive treatments on insulin signalling in lympho-monocytes of essential hypertensive patients: A pilot study

Carolina De Ciuceis, Vincenzo Flati, Claudia Rossini, Anna Rufo, Enzo Porteri, Jacopo Di Gregorio, Beatrice Petroboni, Elisa La Boria, Carlotta Donini, Evasio Pasini, Enrico Agabiti Rosei, Damiano Rizzoni

Research output: Contribution to journalArticlepeer-review

Abstract

It was previously demonstrated that metabolic syndrome in humans is associated with an impairment of insulin signalling in circulating mononuclear cells. At least in animal models of hypertension, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) may correct alterations of insulin signalling in the skeletal muscle. In the first study, we investigated the effects of a 3-month treatment with an ARB with additional PPARγ agonist activity, telmisartan, or with a dihydropyridine calcium channel blocker, nifedipine, on insulin signalling in patients with mild-moderate essential hypertension. Insulin signalling was evaluated in mononuclear cells by isolating them through Ficoll-Paque density gradient centrifugation and protein analysis by Western Blot. An increased expression of mTOR and of phosphorylated (active) mTOR (p-mTOR) was observed in patients treated with telmisartan, but not in those treated with nifedipine, while both treatments increased the cellular expression of glucose transporter type 4 (GLUT-4). We also investigated the effects of antihypertensive treatment with two drug combinations on insulin signalling and oxidative stress. Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine. Then they were treated for 6 months with lercanidipine + enalapril or lercanidipine + hydrochlorothiazide. An increased expression of insulin receptor, GLUT-4 and an increased activation of p70S6K1 were observed during treatment with lercanidipine + enalapril but not with lercanidipine + hydrochlorothiazide. In conclusion, telmisartan and nifedipine are both effective in improving insulin signalling in human hypertension; however, telmisartan seems to have broader effects. The combination treatment lercanidipine + enalapril seems to be more effective than lercanidipine + hydrochlorothiazide in activating insulin signalling in human lympho-monocytes.

Original languageEnglish
Pages (from-to)330-338
Number of pages9
JournalBlood Pressure
Volume23
Issue number6
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Enalapril hydrochlorothiazide
  • GLUT-4
  • Insulin lymphocites
  • Insulin signalling
  • Lercanidipine
  • Monocytes
  • MTOR
  • Nifedipine
  • Telmisartan

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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