Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats
Abstract.: To clarify the role of dipeptidyl peptidase-4 (DPP-4) inhibition in vascular tissues, we compared the effects of the poorly tissue-penetrative DPP-4 inhibitor sitagliptin to the highly tissue-penetrative DPP-4 inhibitor linagliptin in Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rat...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319301082 |
| _version_ | 1819062581480914944 |
|---|---|
| author | Shinji Takai Hiroshi Sakonjo Denan Jin |
| author_facet | Shinji Takai Hiroshi Sakonjo Denan Jin |
| author_sort | Shinji Takai |
| collection | DOAJ |
| description | Abstract.: To clarify the role of dipeptidyl peptidase-4 (DPP-4) inhibition in vascular tissues, we compared the effects of the poorly tissue-penetrative DPP-4 inhibitor sitagliptin to the highly tissue-penetrative DPP-4 inhibitor linagliptin in Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats were orally treated with placebo, sitagliptin (10 mg/kg), or linagliptin (3 mg/kg) for 4 weeks. Sitagliptin and linagliptin produced equivalent decreases in blood glucose concentrations and increased plasma insulin concentrations during oral glucose tolerance tests after the first and the last treatments. In isolated arteries, acetylcholine-induced vascular relaxation was significantly augmented by sitagliptin and linagliptin, with significantly stronger relaxation observed with linagliptin compared to sitagliptin. Vascular DPP-4 activity was attenuated by these drugs, with linagliptin producing significant greater attenuation than sitagliptin. Vascular malondialdehide levels were significantly lower with linagliptin compared to sitagliptin. Significantly greater attenuation of vascular gene expressions of p22phox and monocyte chemoattractant protein-1 by linagliptin, compared with sitagliptin, was also observed. In conclusion, the superior vascular protection by linagliptin compared with sitagliptin was unrelated to the regulation of circulating glucose and insulin levels, and the stronger vascular DPP-4 inhibition by linagliptin may contribute to the mechanism of vascular protection. Keywords:: diabetes, dipeptidyl peptidase 4, inhibitor, vascular tissue, penetration |
| first_indexed | 2024-12-21T15:01:03Z |
| format | Article |
| id | doaj.art-30569bcc7b1246eba2047f51e1c0470a |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-21T15:01:03Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-30569bcc7b1246eba2047f51e1c0470a2022-12-21T18:59:35ZengElsevierJournal of Pharmacological Sciences1347-86132014-01-011254386393Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty RatsShinji Takai0Hiroshi Sakonjo1Denan Jin2Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki city, Osaka 569-8686, Japan; Corresponding author. pha010@art.osaka-med.ac.jpShiga Research Center, Nissei BILIS, 555 Minakuchi-cho, Shiga 528-0052, JapanDepartment of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki city, Osaka 569-8686, JapanAbstract.: To clarify the role of dipeptidyl peptidase-4 (DPP-4) inhibition in vascular tissues, we compared the effects of the poorly tissue-penetrative DPP-4 inhibitor sitagliptin to the highly tissue-penetrative DPP-4 inhibitor linagliptin in Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats were orally treated with placebo, sitagliptin (10 mg/kg), or linagliptin (3 mg/kg) for 4 weeks. Sitagliptin and linagliptin produced equivalent decreases in blood glucose concentrations and increased plasma insulin concentrations during oral glucose tolerance tests after the first and the last treatments. In isolated arteries, acetylcholine-induced vascular relaxation was significantly augmented by sitagliptin and linagliptin, with significantly stronger relaxation observed with linagliptin compared to sitagliptin. Vascular DPP-4 activity was attenuated by these drugs, with linagliptin producing significant greater attenuation than sitagliptin. Vascular malondialdehide levels were significantly lower with linagliptin compared to sitagliptin. Significantly greater attenuation of vascular gene expressions of p22phox and monocyte chemoattractant protein-1 by linagliptin, compared with sitagliptin, was also observed. In conclusion, the superior vascular protection by linagliptin compared with sitagliptin was unrelated to the regulation of circulating glucose and insulin levels, and the stronger vascular DPP-4 inhibition by linagliptin may contribute to the mechanism of vascular protection. Keywords:: diabetes, dipeptidyl peptidase 4, inhibitor, vascular tissue, penetrationhttp://www.sciencedirect.com/science/article/pii/S1347861319301082 |
| spellingShingle | Shinji Takai Hiroshi Sakonjo Denan Jin Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats Journal of Pharmacological Sciences |
| title | Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats |
| title_full | Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats |
| title_fullStr | Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats |
| title_full_unstemmed | Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats |
| title_short | Significance of Vascular Dipeptidyl Peptidase-4 Inhibition on Vascular Protection in Zucker Diabetic Fatty Rats |
| title_sort | significance of vascular dipeptidyl peptidase 4 inhibition on vascular protection in zucker diabetic fatty rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319301082 |
| work_keys_str_mv | AT shinjitakai significanceofvasculardipeptidylpeptidase4inhibitiononvascularprotectioninzuckerdiabeticfattyrats AT hiroshisakonjo significanceofvasculardipeptidylpeptidase4inhibitiononvascularprotectioninzuckerdiabeticfattyrats AT denanjin significanceofvasculardipeptidylpeptidase4inhibitiononvascularprotectioninzuckerdiabeticfattyrats |