Effect of sitagliptin plus metformin on β-cell function, islet integrity and islet gene expression in Zucker diabetic fatty rats.
Han, SJ; Choi, SE; Kang, Y; Jung, JG; Yi, SA; Kim, HJ; Lee, KW; Kim, DJ
Diabetes research and clinical practice, 92(2):213-222, 2011
Diabetes research and clinical practice
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.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
Total Visit :5,289,129
Total Download :2,234,666
Today View :1,502
Ajou University Medical Information & Media Center 164 Worldcup-ro Yeongtong-gu Suwon 16499 Korea / TEL : 031-219-5312 / FAX : 031-219-5314 Copyright (c) Ajou University Medical Information & Media Center All Rights Reserved. AJOU Open Repository는 국립중앙도서관 OAK 보급사업으로 구축되었습니다.