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  • 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)
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)
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)
skos:notation
  • RIV/00023001:_____/13:00058666!RIV14-GA0-00023001
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GAP304/10/0762)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 71930
http://linked.open...ai/riv/idVysledku
  • RIV/00023001:_____/13:00058666
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • model; sitagliptin; exendin-4; onset; mouse; combination therapy; regulatory t-cells (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [6DAEF0D92BD4]
http://linked.open...i/riv/nazevZdroje
  • Folia biologica (Praha)
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 59
http://linked.open...iv/tvurceVysledku
  • Saudek, František
  • Zacharovová, Klára
  • Dovolilová, Eva
  • Vargová, Lenka
  • Vojtová, Lenka
  • Cimburek, Z.
http://linked.open...ain/vavai/riv/wos
  • 000322419900004
issn
  • 0015-5500
number of pages
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