Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury
Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tanaka, Yuki [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2016transfer abstract |
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| Umfang: |
7 |
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| Übergeordnetes Werk: |
Enthalten in: Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag - Zhang, Zhikun ELSEVIER, 2019, BBRC, Orlando, Fla |
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| Übergeordnetes Werk: |
volume:470 ; year:2016 ; number:3 ; day:12 ; month:02 ; pages:539-545 ; extent:7 |
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| DOI / URN: |
10.1016/j.bbrc.2016.01.109 |
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| 520 | |a Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. | ||
| 520 | |a Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. | ||
| 650 | 7 | |a Proximal tubular cell |2 Elsevier | |
| 650 | 7 | |a Diabetic nephropathy |2 Elsevier | |
| 650 | 7 | |a DPP–4 inhibitors |2 Elsevier | |
| 650 | 7 | |a Free fatty acid |2 Elsevier | |
| 650 | 7 | |a Albuminuria |2 Elsevier | |
| 700 | 1 | |a Kume, Shinji |4 oth | |
| 700 | 1 | |a Chin-Kanasaki, Masami |4 oth | |
| 700 | 1 | |a Araki, Hisazumi |4 oth | |
| 700 | 1 | |a Araki, Shin-ichi |4 oth | |
| 700 | 1 | |a Ugi, Satoshi |4 oth | |
| 700 | 1 | |a Sugaya, Takeshi |4 oth | |
| 700 | 1 | |a Uzu, Takashi |4 oth | |
| 700 | 1 | |a Maegawa, Hiroshi |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Academic Press |a Zhang, Zhikun ELSEVIER |t Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag |d 2019 |d BBRC |g Orlando, Fla |w (DE-627)ELV002811154 |
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10.1016/j.bbrc.2016.01.109 doi GBVA2016020000027.pica (DE-627)ELV024837660 (ELSEVIER)S0006-291X(16)30109-7 DE-627 ger DE-627 rakwb eng 570 570 DE-600 670 VZ 51.60 bkl 58.45 bkl Tanaka, Yuki verfasserin aut Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury 2016transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Proximal tubular cell Elsevier Diabetic nephropathy Elsevier DPP–4 inhibitors Elsevier Free fatty acid Elsevier Albuminuria Elsevier Kume, Shinji oth Chin-Kanasaki, Masami oth Araki, Hisazumi oth Araki, Shin-ichi oth Ugi, Satoshi oth Sugaya, Takeshi oth Uzu, Takashi oth Maegawa, Hiroshi oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 https://doi.org/10.1016/j.bbrc.2016.01.109 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 470 2016 3 12 0212 539-545 7 045F 570 |
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10.1016/j.bbrc.2016.01.109 doi GBVA2016020000027.pica (DE-627)ELV024837660 (ELSEVIER)S0006-291X(16)30109-7 DE-627 ger DE-627 rakwb eng 570 570 DE-600 670 VZ 51.60 bkl 58.45 bkl Tanaka, Yuki verfasserin aut Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury 2016transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Proximal tubular cell Elsevier Diabetic nephropathy Elsevier DPP–4 inhibitors Elsevier Free fatty acid Elsevier Albuminuria Elsevier Kume, Shinji oth Chin-Kanasaki, Masami oth Araki, Hisazumi oth Araki, Shin-ichi oth Ugi, Satoshi oth Sugaya, Takeshi oth Uzu, Takashi oth Maegawa, Hiroshi oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 https://doi.org/10.1016/j.bbrc.2016.01.109 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 470 2016 3 12 0212 539-545 7 045F 570 |
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10.1016/j.bbrc.2016.01.109 doi GBVA2016020000027.pica (DE-627)ELV024837660 (ELSEVIER)S0006-291X(16)30109-7 DE-627 ger DE-627 rakwb eng 570 570 DE-600 670 VZ 51.60 bkl 58.45 bkl Tanaka, Yuki verfasserin aut Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury 2016transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Proximal tubular cell Elsevier Diabetic nephropathy Elsevier DPP–4 inhibitors Elsevier Free fatty acid Elsevier Albuminuria Elsevier Kume, Shinji oth Chin-Kanasaki, Masami oth Araki, Hisazumi oth Araki, Shin-ichi oth Ugi, Satoshi oth Sugaya, Takeshi oth Uzu, Takashi oth Maegawa, Hiroshi oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 https://doi.org/10.1016/j.bbrc.2016.01.109 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 470 2016 3 12 0212 539-545 7 045F 570 |
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10.1016/j.bbrc.2016.01.109 doi GBVA2016020000027.pica (DE-627)ELV024837660 (ELSEVIER)S0006-291X(16)30109-7 DE-627 ger DE-627 rakwb eng 570 570 DE-600 670 VZ 51.60 bkl 58.45 bkl Tanaka, Yuki verfasserin aut Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury 2016transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Proximal tubular cell Elsevier Diabetic nephropathy Elsevier DPP–4 inhibitors Elsevier Free fatty acid Elsevier Albuminuria Elsevier Kume, Shinji oth Chin-Kanasaki, Masami oth Araki, Hisazumi oth Araki, Shin-ichi oth Ugi, Satoshi oth Sugaya, Takeshi oth Uzu, Takashi oth Maegawa, Hiroshi oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 https://doi.org/10.1016/j.bbrc.2016.01.109 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 470 2016 3 12 0212 539-545 7 045F 570 |
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10.1016/j.bbrc.2016.01.109 doi GBVA2016020000027.pica (DE-627)ELV024837660 (ELSEVIER)S0006-291X(16)30109-7 DE-627 ger DE-627 rakwb eng 570 570 DE-600 670 VZ 51.60 bkl 58.45 bkl Tanaka, Yuki verfasserin aut Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury 2016transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. Proximal tubular cell Elsevier Diabetic nephropathy Elsevier DPP–4 inhibitors Elsevier Free fatty acid Elsevier Albuminuria Elsevier Kume, Shinji oth Chin-Kanasaki, Masami oth Araki, Hisazumi oth Araki, Shin-ichi oth Ugi, Satoshi oth Sugaya, Takeshi oth Uzu, Takashi oth Maegawa, Hiroshi oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 https://doi.org/10.1016/j.bbrc.2016.01.109 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 470 2016 3 12 0212 539-545 7 045F 570 |
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Enthalten in Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag Orlando, Fla volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 |
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Enthalten in Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag Orlando, Fla volume:470 year:2016 number:3 day:12 month:02 pages:539-545 extent:7 |
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Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag |
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Tanaka, Yuki @@aut@@ Kume, Shinji @@oth@@ Chin-Kanasaki, Masami @@oth@@ Araki, Hisazumi @@oth@@ Araki, Shin-ichi @@oth@@ Ugi, Satoshi @@oth@@ Sugaya, Takeshi @@oth@@ Uzu, Takashi @@oth@@ Maegawa, Hiroshi @@oth@@ |
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Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury |
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Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. |
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Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. |
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Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. |
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