Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 5-8%. Type 2 diabetes and cardiovascular disease (CVD) are its long-term complications. Targeted therapies addressing both these complications together are lacking. Glucagon like peptide-1 (GLP-1) agonists that are used to treat type 2 diabetes mellitus have beneficial effects on the cardiovascular system. Hence we hypothesized that a GLP-1 agonist would improve both cardiovascular and metabolic outcomes in PCOS. To test this hypothesis, we used an established rat model of PCOS. Prepubertal female Sprague Dawley rats were sham-implanted or implanted s.c. with dihydrotestosterone (DHT) pellets (90 day release; 83 mu g/day). At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2mg/kg s.c twice daily) for 4 weeks. Subgroups of rats were implanted with telemeters between 12-13 weeks of age to monitor blood pressure. DHT implanted rats had irregular estrus cycles and were significantly heavier than the control females at 12 weeks (mean +/- SEM 251.9 +/- 3.4 vs 216.8 +/- 3.4 respectively; p<0.05) and 4 weeks of treatment with liraglutide in DHT treated rats significantly decreased body weight (mean +/- SEM 294.75 +/- 3.2 in DHT+ saline vs 276.25 +/- 2.7 in DHT+ liraglutide group respectively; p<0.01). Liraglutide treatment in the DHT implanted rats significantly improved glucose excursion during oral glucose tolerance test (area under the curve: DHT+ saline 28674 +/- 310 vs 24990 +/- 420 in DHT+ liraglutide p<0.01). DHT rats were hypertensive and liraglutide treatment significantly improved mean arterial pressure. These results suggest that GLP-1 treatment could improve DHT-induced metabolic and blood pressure deficits associated with PCOS.
基金:
National Institutes of Health from the Office of Research on Women's Health [K12HD065879]
第一作者单位:[1]Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA
通讯作者:
推荐引用方式(GB/T 7714):
Hoang Vanessa,Bi Jiangjiang,Mohankumar Sheba M.,et al.Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome[J].PLOS ONE.2015,10(5):doi:10.1371/journal.pone.0126119.
APA:
Hoang, Vanessa,Bi, Jiangjiang,Mohankumar, Sheba M.&Vyas, Arpita K..(2015).Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome.PLOS ONE,10,(5)
MLA:
Hoang, Vanessa,et al."Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome".PLOS ONE 10..5(2015)