Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Sadaaki; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi; Makino, Hírofumi

doi:10.1016/j.bbrc.2013.12.049

Cited by 93 publications

(65 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have shown that cardiomyoblasts express TLR-4, through which LPS exerts a adverse effect mediated by NF-κB signaling, resulting in decreased cardiomyocyte contractility (23,24). It has been reported that the regulation of NF-κB was involved in the amelioration of inflammatory responses by DPP-4 inhibitor (25). Several studies also demonstrated that DPP-4 inhibitor has beneficial effects on cardiovascular system and gain the ability to improve renal microvasculature (26,27).…”

Section: A B Cmentioning

confidence: 98%

Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition

Lin¹,

Lin²

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Glucagon-like peptide-1 (GLP-1) and GLP-1 receptors (GLP-1Rs) are responsible for glucose homeostasis, and have been shown to reduce inflammation in preclinical studies. The aim of the present study was to determine whether sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), as a GLP-1 receptor agonist, exerts an anti-inflammatory effect on cardiomyoblasts during lipopolysaccharide (LPS) stimulation. Exposure to LPS increased the expression levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and IL-1β in H9c2 cells, and also resulted in elevations in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) nuclear translocation. Treatment with the DPP-4 inhibitor sitagliptin dose-dependently downregulated the mRNA levels of IL-6, COX-2 and iNOS in LPS-stimulated H9c2 cells. In addition, sitagliptin inhibited the increased protein expression of IL-6, TNF-α and IL-1β. NF-κB mRNA expression was reduced and its translocation to the nucleus was suppressed by treatment with sitagliptin. The present results demonstrated that sitagliptin exerts a beneficial effect on cardiomyoblasts exposed to LPS by inhibiting expression of inflammatory mediators and suppressing NF-κB activation. These findings indicate that the DPP-4 inhibitor sitagliptin may serve a function in cardiac remodeling attributed to sepsis-induced inflammation.

show abstract

Section: A B Cmentioning

confidence: 98%

Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition

Lin¹,

Lin²

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Additionally, oxidative stress and inflammation were observed in the kidneys of diabetic rats. 19,20,22 Thus, STZ-induced diabetic rats may be useful as a model of early changes in diabetic nephropathy. However, the hyperglycemia-induced morphological changes in the kidneys of this rat model were less significant than those observed in the STZ-induced diabetic mice.…”

Section: Stz-induced Diabetic Ratsmentioning

confidence: 99%

Rodent models of diabetic nephropathy: their utility and limitations

Kitada¹,

Ogura²,

Koya³

2016

IJNRD

200

151

View full text Add to dashboard Cite

Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy.

show abstract

“…Введение вилдаглиптина спо-собствовало снижению содержания TGF-β1 и тормозило развитие фиброза клубочков и интерстиция [51]. Аналог вилдаглиптина PKF275-055 в данной модели снижал экс-прессию генов ICAM-1 и TNFα, активность NF-κВ; дан-ные эффекты не зависели от изменений гликемии [52].…”

Section: ингибиторы дпп-4unclassified

Incretin-based therapy: renal effects

Korbut¹,

Климонтов²

2016

Diabetes mellitus

View full text Add to dashboard Cite

© Сахарный диабет, 2016ерапия, основанная на модификации эффекта инкретиновых гормонов, -сравнительно новое направление в лечении сахарного диабета 2 типа (СД2). Аналоги глюкагоноподобного пептида 1 типа (ГПП-1) и ингибиторы дипептидилпептидазы 4 типа (ДПП-4) обладают широким спектром фармакологиче-ского действия, включающего гликемические и неглике-мические эффекты. В последние годы большой интерес вызывает способность препаратов данных классов вли-ять на развитие осложнений СД. В настоящем обзоре обобщены результаты экспериментальных и клиниче-ских исследований, посвященных изучению эффектов агонистов ГПП-1 и ингибиторов ДПП-4 на структурно-функциональные изменения в почках при СД. Поиск источников проведен в базах данных Medline/PubMed, Scopus, Web of Science, eLibrary, ClinicalTrials.gov, а также в электронных базах материалов конгрессов Американ-ской диабетической ассоциации (ADA) и Европейской ассоциации по изучению сахарного диабета (EASD). Представлены результаты оригинальных исследований и мета-анализов, опубликованных на русском и англий-ском языках, преимущественно в период 2011-2015 гг. Почка как орган-мишень и место деградации инкретиновых гормонов

show abstract

Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

Cited by 93 publications

References 24 publications

Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition

Sitagliptin attenuates inﬂammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition

Rodent models of diabetic nephropathy: their utility and limitations

Incretin-based therapy: renal effects

Contact Info

Product

Resources

About