title: Liraglutide improves hypertension and metabolic perturbation in a rat model of polycystic ovarian syndrome.
abstract: 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 μg/day). At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2 mg/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.
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hoang
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, United States of America; Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Sheba M
authors.initials: SM
authors.lastname: Mohankumar
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Arpita K
authors.initials: AK
authors.lastname: Vyas
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000069450:Liraglutide / Q000494:pharmacology / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013686:Telemetry; D015430:Weight Gain / Q000187:drug effects
chemical_list: D013196:Dihydrotestosterone; D000069450:Liraglutide; D002784:Cholesterol; D005947:Glucose