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Description
| - Sitagliptin is a dipeptidyl peptidase IV (DPP-IV) inhibitor that exerts an anti-hyperglycaemic effect by preventing degradation of glucagon-like peptide 1 with subsequent beta-cell stimulation and potential regeneration. We tested whether sitagliptin therapy in symptomatic non-obese diabetic (NOD) mice would lead to changes in the immune cell profile, improve beta-cell survival and induce diabetes remission. Flow cytometry analysis of immune cells in the spleen and peripheral lymph nodes, immunohistology of the pancreas and DPP-IV activity were investigated in diabetic NOD mice, either treated or non-treated with sitagliptin, at 0, 7, 14 and 28 days after hyperglycaemia onset, and in non-diabetic NOD controls. While compared to diabetic controls sitagliptin prevented increase of the CD8(+)/CD4(+) ratio in pancreatic nodes after four weeks (0.443 +/- 0.067 vs. 0.544 +/- 0.131; P < 0.05), the population of Tregs in lymph nodes increased from day 0 to 28 in both treated and non-treated diabetic groups (8 +/- 1.76 vs. 13.45 +/- 5.07 % and 8 +/- 1.76 vs. 13.19 +/- 5.58 %, respectively). The severity of islet infiltration was similar in both diabetic groups and decreased in parallel with p-cell loss. Surprisingly, sitagliptin blocked the DPP-IV activity only temporarily (on day 7, 277.68 +/- 89.2 vs. 547.40 +/- 94.04 ng/ml in the diabetic control group) with no apparent effect later on. In conclusion, sitagliptin administered after the onset of overt hyperglycaemia in NOD mice had only a marginal immunological effect and did not lead to diabetes remission. Failure to block DPP-IV over time represents an important finding that requires further explanation.
- Sitagliptin is a dipeptidyl peptidase IV (DPP-IV) inhibitor that exerts an anti-hyperglycaemic effect by preventing degradation of glucagon-like peptide 1 with subsequent beta-cell stimulation and potential regeneration. We tested whether sitagliptin therapy in symptomatic non-obese diabetic (NOD) mice would lead to changes in the immune cell profile, improve beta-cell survival and induce diabetes remission. Flow cytometry analysis of immune cells in the spleen and peripheral lymph nodes, immunohistology of the pancreas and DPP-IV activity were investigated in diabetic NOD mice, either treated or non-treated with sitagliptin, at 0, 7, 14 and 28 days after hyperglycaemia onset, and in non-diabetic NOD controls. While compared to diabetic controls sitagliptin prevented increase of the CD8(+)/CD4(+) ratio in pancreatic nodes after four weeks (0.443 +/- 0.067 vs. 0.544 +/- 0.131; P < 0.05), the population of Tregs in lymph nodes increased from day 0 to 28 in both treated and non-treated diabetic groups (8 +/- 1.76 vs. 13.45 +/- 5.07 % and 8 +/- 1.76 vs. 13.19 +/- 5.58 %, respectively). The severity of islet infiltration was similar in both diabetic groups and decreased in parallel with p-cell loss. Surprisingly, sitagliptin blocked the DPP-IV activity only temporarily (on day 7, 277.68 +/- 89.2 vs. 547.40 +/- 94.04 ng/ml in the diabetic control group) with no apparent effect later on. In conclusion, sitagliptin administered after the onset of overt hyperglycaemia in NOD mice had only a marginal immunological effect and did not lead to diabetes remission. Failure to block DPP-IV over time represents an important finding that requires further explanation. (en)
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Title
| - The effects of DPP-IV inhibition in NOD mice with overt diabetes
- The effects of DPP-IV inhibition in NOD mice with overt diabetes (en)
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skos:prefLabel
| - The effects of DPP-IV inhibition in NOD mice with overt diabetes
- The effects of DPP-IV inhibition in NOD mice with overt diabetes (en)
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skos:notation
| - RIV/00023001:_____/13:00058666!RIV14-GA0-00023001
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/00023001:_____/13:00058666
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - model; sitagliptin; exendin-4; onset; mouse; combination therapy; regulatory t-cells (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Saudek, František
- Zacharovová, Klára
- Dovolilová, Eva
- Vargová, Lenka
- Vojtová, Lenka
- Cimburek, Z.
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http://linked.open...ain/vavai/riv/wos
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issn
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number of pages
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