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Effect of sitagliptin plus metformin on β-cell function, islet integrity and islet gene expression in Zucker diabetic fatty rats.

Authors
Han, SJ; Choi, SE; Kang, Y; Jung, JG; Yi, SA; Kim, HJ; Lee, KW; Kim, DJ
Citation
Diabetes research and clinical practice, 92(2):213-222, 2011
Journal Title
Diabetes research and clinical practice
ISSN
0168-82271872-8227
Abstract
AIM: The combination of metformin and a dipeptidyl peptidase 4 (DPP-4) inhibitor has been shown to be an effective, safe, and well-tolerated treatment for type 2 diabetes. We evaluated β-cell function and morphological changes in islets in Zucker diabetic fatty (ZDF) rats following combined therapy with sitagliptin and metformin and investigated the expression of potentially relevant genes using cDNA microarrays.



METHODS: Nine-week-old ZDF rats were randomly divided into four treatment groups: no treatment (control); sitagliptin; metformin, and sitagliptin plus metformin. After 5 weeks of treatment, an oral glucose tolerance test was performed and plasma levels of active GLP-1 and islet morphology and gene expression were assessed.



RESULTS: Combination therapy reduced fasting glucose and postprandial plasma glucose levels and increased active GLP-1 levels, compared with monotherapy. Combination therapy also increased insulin secretion, the proportion of small islets, and the intensity of insulin staining. Furthermore, it increased the expression of genes involved in cell survival and growth and downregulated apoptosis-associated genes, relative to monotherapy.



CONCLUSIONS: Combination treatment with sitagliptin and metformin preserved β-cell function and β-cell integrity in ZDF rats. This may be associated with the transcriptional activation of anti-apoptotic and pro-survival genes, as well as the suppression of pro-apoptotic genes.
MeSH terms
AnimalsCaspase 3/metabolismFluorescent Antibody TechniqueGlucagon-Like Peptide 1/metabolismGlucose Tolerance TestHypoglycemic Agents/*pharmacologyInsulin-Secreting Cells/*drug effects/*metabolismMaleMetformin/*pharmacologyOligonucleotide Array Sequence AnalysisPyrazines/*pharmacologyRatsRats, ZuckerReceptor, IGF Type 1/metabolismReverse Transcriptase Polymerase Chain ReactionTriazoles/*pharmacologyets-Domain Protein Elk-1/metabolism
DOI
10.1016/j.diabres.2011.01.016
PMID
21345512
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
한, 승진강, 엽김, 혜진이, 관우김, 대중
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