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The DPP-4 Inhibitor Vildagliptin Increases Pancreatic Beta Cell Mass In Neonatal Rats

Duttaroy, Alokesh and Voelker, Frank and Merriam, Kimberly and Zhang, Xia and Ren, Xianglin and Subramanian, Kala and Hughes, Thomas and Burkey, Bryan (2011) The DPP-4 Inhibitor Vildagliptin Increases Pancreatic Beta Cell Mass In Neonatal Rats. European Journal of Pharmacology, 650 (2-3). pp. 703-707. ISSN 0014-2999

Abstract

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 (60 mg/kg) or vehicle once daily for 19 days 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 and 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 12 days 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.

Item Type: Article
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Keywords: DPP-4, Vildagliptin, Apoptosis, Beta cell mass, BrdU-incorporation, glucagon, immunohistochemistry, insulin, morphometry, neonatal rats, pancreatic insulin content
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/1914

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