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Statements

Subject Item
n2:RIV%2F00023001%3A_____%2F13%3A00058666%21RIV14-GA0-00023001
rdf:type
skos:Concept n13:Vysledek
rdfs:seeAlso
http://fb.cuni.cz/file/5689/FB2013A0016.pdf
dcterms: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.
dcterms: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
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
skos:notation
RIV/00023001:_____/13:00058666!RIV14-GA0-00023001
n13:predkladatel
n14:ico%3A00023001
n3:aktivita
n8:P
n3:aktivity
P(GAP304/10/0762)
n3:cisloPeriodika
3
n3:dodaniDat
n5:2014
n3:domaciTvurceVysledku
n4:4620747 n4:1618954 n4:1404962 n4:2898616 n4:3752437
n3:druhVysledku
n6:J
n3:duvernostUdaju
n19:S
n3:entitaPredkladatele
n15:predkladatel
n3:idSjednocenehoVysledku
71930
n3:idVysledku
RIV/00023001:_____/13:00058666
n3:jazykVysledku
n12:eng
n3:klicovaSlova
model; sitagliptin; exendin-4; onset; mouse; combination therapy; regulatory t-cells
n3:klicoveSlovo
n7:sitagliptin n7:exendin-4 n7:regulatory%20t-cells n7:model n7:onset n7:combination%20therapy n7:mouse
n3:kodStatuVydavatele
CZ - Česká republika
n3:kontrolniKodProRIV
[6DAEF0D92BD4]
n3:nazevZdroje
Folia biologica (Praha)
n3:obor
n18:FB
n3:pocetDomacichTvurcuVysledku
5
n3:pocetTvurcuVysledku
6
n3:projekt
n17:GAP304%2F10%2F0762
n3:rokUplatneniVysledku
n5:2013
n3:svazekPeriodika
59
n3:tvurceVysledku
Cimburek, Z. Vojtová, Lenka Dovolilová, Eva Saudek, František Vargová, Lenka Zacharovová, Klára
n3:wos
000322419900004
s:issn
0015-5500
s:numberOfPages
7