scholarly journals Endogenous dipeptidyl peptidase IV modulates skeletal muscle arteriolar diameter in rats

2018 ◽  
Vol 6 (2) ◽  
pp. e13564 ◽  
Author(s):  
Leslie E. Neidert ◽  
Mohammed Al-Tarhuni ◽  
Daniel Goldman ◽  
Heidi A. Kluess ◽  
Dwayne N. Jackson
Keyword(s):  
Skeletal Muscle ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Arteriolar Diameter

scholarly journals Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 1069-1069
Author(s):  
Michael Boschmann ◽  
Stefan Engeli ◽  
Kerstin Dobberstein ◽  
Petra Budziarek ◽  
Anke Strauss ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Standardized Test ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Lipid Mobilization ◽  
Postprandial Lipid

Abstract Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study. Setting: Academic clinical research center. Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m2. Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine

2017 ◽  
pp. 4-12
Author(s):  
Н.Н. Хлебникова ◽  
Н.А. Крупина
Keyword(s):  
Forced Swimming Test ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Forced Swimming ◽  
Face Validity ◽  
Neonatal Exposure ◽  
Depressive State ◽  
Serum Corticosterone ◽  
Old Rats ◽  
Swimming Test

В наших предыдущих исследованиях было показано, что ингибитор пролинспецифической пептидазы дипептидилпептидазы-IV (ДП-IV, EC 3.4.14.5) трипептид дипротин А, введенный крысам в 5-18 постнатальные дни, приводит к развитию у крыс подросткового возраста и взрослых животных эмоционально-мотивационных расстройств. Такие расстройства можно рассматривать как модель смешанного тревожно-депрессивного состояния. Однако специальных исследований по валидности данной модели проведено не было. Цель настоящей работы состояла в проверке влияния трициклического антидепрессанта имипрамина (ИМИ) на депрессивноподобное поведение крыс и уровень кортикостерона в сыворотке крови животных на модели смешанного тревожно-депрессивного состояния. Методика. У крыс в возрасте одного и двух мес. определяли уровень тревожности в автоматизированном тесте «Приподнятый крестообразный лабиринт» и оценивали депрессивноподобное поведение в тесте принудительного плавания. ИМИ вводили взрослым животным в течение 10 дней (20 мг/кг/день, интрагастрально). Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Неонатальное действие дипротина А приводило к повышению тревожности у крыс в возрасте 1 мес. Депрессивноподобное поведение обнаружено у животных в возрасте одного и двух мес. ИМИ нормализовал поведение животных в тесте принудительного плавания и снижал уровень кортикостерона в сыворотке крови крыс. Кроме того, ИМИ снижал вес крыс. Заключение. Результаты исследования свидетельствуют в пользу адекватности модели смешанного тревожно-депрессивного расстройства, возникающего у крыс вследствие действия ингибитора ДП-IV дипротина А на второй-третьей неделях постнатального развития, клиническому прообразу заболевания по критериям «внешней схожести», прогностической и конструкционной валидности. Previously, we have shown that the inhibitor of proline-specific peptidase, dipeptidyl peptidase-IV (DP-IV, EC 3.4.14.5), tripeptide diproptin A administered on postnatal days 5-18 induced emotional and motivational disorders in adolescent and adult rats. These disorders can be considered a model of a mixed anxiety-depression-like disorder. However, validation studies of this model are not available. The aim of this work was to test the effect of the tricyclic antidepressant, imipramine (IMI), on depressive-like behavior in rats and the level of serum corticosterone using the model of mixed anxiety-depressive state. Methods. The level of anxiety was assessed by the automated Elevated Plus Maze test and the depressive-like behavior was evaluated by the forced swimming test in one- and two-month old rats. IMI was administered to adult animals for ten days (20 mg/kg a day, intragastrically). Serum corticosterone concentrations were measured using ELISA. Results. The neonatal exposure to diprotin A increased anxiety in one-month old rats. The depressive-like behavior was observed in animals aged one and two months. IMI normalized behavior of animals in the forced swimming test and reduced serum levels of corticosterone. Also, IMI reduced body weight of rats. Conclusion. The results of the study evidenced adequacy of the model of mixed anxiety-depressive state induced by the DP-IV inhibitor, diprotin A, on the second and third postnatal weeks to the clinical prototype of disease according to criteria of face validity, predictive and construct validity.

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