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The DPP-4 inhibitor vildagliptin increases pancreatic beta cell mass in neonatal rats.
MedLine Citation:
PMID:  21070766     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The present study addressed the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin ((1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine), LAF237) on pancreatic beta cell mass in neonatal rats. Newborn rats were treated orally with vildagliptin (60mg/kg) or vehicle once daily for 19days starting from postnatal day 2. Pancreatic immunohistochemistry and morphometric analysis were performed to evaluate changes in beta cell mass, cell apoptosis (Apoptag stain) and replication (5'-Bromo-2'-deoxyuridine (BrdU)-incorporation) on days 7, 21, and 33. On day 7, an eight-fold increase in BrdU-positive pancreatic beta cells and a 71% decrease in Apoptag-positive cells were observed. On day 21, vildagliptin produced a two-fold increase in pancreatic beta cell mass compared to placebo (0.06±0.01mg vs 0.11±0.02mg, P<0.05). Beta cell mass remained elevated (90%, 0.09±0.02mg vs 0.16±0.03mg, P<0.05) on day 33, twelve days after discontinuing vildagliptin treatment. These data show that the DPP-4 inhibitor vildagliptin increased pancreatic beta cell mass through enhanced beta cell replication and reduced apoptosis. The increased beta cell mass was sustained for 12days after vildagliptin washout. This study demonstrates that DPP-4 inhibitors can elicit beneficial effects on beta cell turnover that could help to prevent or retard the progression of type 2 diabetes.
Authors:
Alokesh Duttaroy; Frank Voelker; Kimberley Merriam; Xia Zhang; Xianglin Ren; Kala Subramanian; Thomas E Hughes; Bryan F Burkey
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Publication Detail:
Type:  Journal Article     Date:  2010-11-09
Journal Detail:
Title:  European journal of pharmacology     Volume:  650     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  703-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
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