Unknown

Dataset Information

0

Sitagliptin (MK0431) inhibition of dipeptidyl peptidase IV decreases nonobese diabetic mouse CD4+ T-cell migration through incretin-dependent and -independent pathways.


ABSTRACT:

Objective

Treatment of NOD mice with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin preserved islet transplants through a pathway involving modulation of splenic CD4(+) T-cell migration. In the current study, effects of sitagliptin on migration of additional subsets of CD4(+) T-cells were examined and underlying molecular mechanisms were further defined.

Research design and methods

Effects of sitagliptin on migration of NOD mouse splenic, thymic, and lymph node CD4(+) T-cells were determined. Signaling modules involved in DPP-IV-, Sitagliptin- and incretin-mediated modulation of CD4(+) T-cell migration were studied using Western blot and Rac1 and nuclear factor-kappaB (NF-kappaB) activity assays.

Results

Migration of splenic and lymph node CD4(+) T-cells of diabetic NOD mice was reduced by sitagliptin treatment. In vitro treatment of splenic, but not thymic or lymph node CD4(+) T-cells, from nondiabetic NOD mice with soluble (s) DPP-IV increased migration. Sitagliptin abolished sDPP-IV effects on splenic CD4(+) T-cell migration, whereas incretins decreased migration of lymph node, but not splenic, CD4(+) T-cells. Splenic CD4(+) T-cells demonstrating increased in vitro migration in response to sDPP-IV and lymph node CD4(+) T-cells that were nonresponsive to incretins selectively infiltrated islets of NOD mice, after injection. Sitagliptin decreases migration of splenic CD4(+) T-cells through a pathway involving Rac1/vasodilator-stimulated phosphoprotein, whereas its inhibitory effects on the migration of lymph node CD4(+) T-cells involve incretin-activation of the NF-kappaB pathway.

Conclusions

Benefits of sitagliptin treatment in diabetic NOD mice may be mediated through selective effects on subpopulations of T-cells that are related to autoimmunity.

SUBMITTER: Kim SJ 

PROVIDER: S-EPMC2889774 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Sitagliptin (MK0431) inhibition of dipeptidyl peptidase IV decreases nonobese diabetic mouse CD4+ T-cell migration through incretin-dependent and -independent pathways.

Kim Su-Jin SJ   Nian Cuilan C   McIntosh Christopher H S CH  

Diabetes 20100405 7


<h4>Objective</h4>Treatment of NOD mice with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin preserved islet transplants through a pathway involving modulation of splenic CD4(+) T-cell migration. In the current study, effects of sitagliptin on migration of additional subsets of CD4(+) T-cells were examined and underlying molecular mechanisms were further defined.<h4>Research design and methods</h4>Effects of sitagliptin on migration of NOD mouse splenic, thymic, and lymph node CD4(+)  ...[more]

Similar Datasets

2011-12-31 | E-MTAB-583 | biostudies-arrayexpress
| S-EPMC3320861 | biostudies-literature
| S-EPMC3043624 | biostudies-literature
| S-EPMC7063094 | biostudies-literature
| S-EPMC1163828 | biostudies-other
| S-EPMC9502781 | biostudies-literature
| S-EPMC5241519 | biostudies-literature
| S-EPMC1462722 | biostudies-literature
| S-EPMC2749928 | biostudies-literature
| S-EPMC3756559 | biostudies-literature