You are not logged in.

One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

Aston-Mourney, Kathryn, Subramanian, Shoba L, Zraika, Sakeneh, Samarasekera, Thanya, Meier, Daniel T, Goldstein, Lynn C and Hull, Rebecca L 2013, One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice, American Journal of Physiology: Endocrinology and Metabolism, vol. 305, no. 4, pp. E475-E484, doi: 10.1152/ajpendo.00025.2013.

Attached Files
Name Description MIMEType Size Downloads

Title One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice
Author(s) Aston-Mourney, Kathryn
Subramanian, Shoba L
Zraika, Sakeneh
Samarasekera, Thanya
Meier, Daniel T
Goldstein, Lynn C
Hull, Rebecca L
Journal name American Journal of Physiology: Endocrinology and Metabolism
Volume number 305
Issue number 4
Start page E475
End page E484
Total pages 10
Publisher American Physiological Society
Place of publication Bethesda, MD
Publication date 2013
ISSN 0193-1849
1522-1555
Keyword(s) DPP-4 inhibitor
Exocrine pancreas pathology
Amyloid
β-cell mass
IAPP
Summary The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing β-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and β-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced β-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates β-cell secretion without increasing amyloid formation and protects against amyloid-induced β-cell loss. This suggests a novel effect of sitagliptin to protect the β-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas.
Language eng
DOI 10.1152/ajpendo.00025.2013
Field of Research 110107 Metabolic Medicine
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2013, American Physiological Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30059481

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 20 times in TR Web of Science
Scopus Citation Count Cited 21 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 213 Abstract Views, 2 File Downloads  -  Detailed Statistics
Created: Tue, 14 Jan 2014, 11:30:08 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.