title: The dipeptidyl peptidase-4 inhibitor teneligliptin improved endothelial dysfunction and insulin resistance in the SHR/NDmcr-cp rat model of metabolic syndrome.
abstract: Diabetes mellitus, hypertension and metabolic syndrome are major risk factors for the occurrence of cardiovascular events. In this study, we used spontaneous hypertensive rat (SHR)/NDmcr-cp (cp/cp) (SHRcp) rats as a model for metabolic syndrome to examine the effects of dipeptidyl peptidase (DPP)-4 inhibition on hypertension, glucose metabolism and endothelial dysfunction. First, we confirmed that SHRcp rats showed very severe obesity, hypertension and endothelial dysfunction phenotypes from 14 to 54 weeks of age. Next, we examined whether the DPP-4 inhibitor teneligliptin (10 mg kg(-1) per day per os for 12 weeks) could modify any of these phenotypes. Treatment with teneligliptin significantly improved hyperglycemia and insulin resistance, as evidenced by an oral glucose tolerance test and homeostasis model assessment for insulin resistance, respectively. Teneligliptin showed no effects on systolic blood pressure or heart rate. In regard to endothelial function, the vasodilator response to acetylcholine was significantly impaired in SHRcp rats when compared with WKY rats. Long-term treatment with teneligliptin significantly attenuated endothelial dysfunction through the upregulation of endothelium-derived nitric oxide synthase mRNA. These results demonstrate that long-term treatment with teneligliptin significantly improved endothelial dysfunction and glucose metabolism in a rat model of metabolic syndrome, suggesting that teneligliptin treatment might be beneficial for patients with hypertension and/or diabetes.
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Zhengda
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Research Department, NISSEI BILIS Co. Ltd., Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimosato
authors.affiliation: Research Department, NISSEI BILIS Co. Ltd., Shiga, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Moritani
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koriyama
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tenma
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000375:Aging; D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; D053778:Thiazolidines; D005947:Glucose