Effect of antihypertensive treatments on insulin signalling in lympho-monocytes of essential hypertensive patients: a pilot study.
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.
Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia , Italy.
Carolina
C
De Ciuceis
Vincenzo
V
Flati
Claudia
C
Rossini
Anna
A
Rufo
Enzo
E
Porteri
Jacopo
J
Di Gregorio
Beatrice
B
Petroboni
Elisa
E
La Boria
Carlotta
C
Donini
Evasio
E
Pasini
Enrico
E
Agabiti Rosei
Damiano
D
Rizzoni
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D000075222:Essential Hypertension; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004338:Drug Combinations; D051275:Glucose Transporter Type 4; D007328:Insulin; D004656:Enalapril; D058570:TOR Serine-Threonine Kinases; D009543:Nifedipine; C060343:lercanidipine
GLUT-4; Insulin signalling; Telmisartan; enalapril hydrochlorothiazide; insulin lymphocites; lercanidipine; mTOR; monocytes; nifedipine