| Combination of TS-021 with metformin improves hyperglycemia and synergistically increases pancreatic β-cell mass in a mouse model of type 2 diabetes. | |
| | |
MedLine Citation:
|
PMID: 21872612 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
AIMS: The objectives of this study were to elucidate the effects of a potent dipeptidyl peptidase (DPP)-IV inhibitor, TS-021, combined with/without metformin on glycemic control and pathological changes in pancreatic islets in high-fat diet and streptozotocin-induced (HFD-STZ) diabetic mice. MAIN METHODS: The anti-diabetic effects of TS-021 and/or metformin in HFD-STZ mice were examined in both acute and chronic treatment studies. In addition, we performed immunohistochemical analysis after repeated administration of TS-021 and/or metformin to HFD-STZ mice twice a day for 5weeks. KEY FINDINGS: In the acute treatment study, TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion. In the chronic treatment study, TS-021 in combination with metformin significantly lowered the glycosylated hemoglobin level, plasma insulin level, and α-cell-to-β-cell area ratio in pancreatic islets. In particular, the combined treatment synergistically increased the insulin-positive area in pancreatic islets from 32.3% in diabetic mice treated with the vehicle to 51.1% (TS-021 alone, 35.3%; metformin alone, 30.6%). SIGNIFICANCE: The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which are thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition). These findings strongly support the rationale for combined treatment with DPP-IV inhibitors plus metformin in clinical practice by clearly demonstrating an anti-diabetic effect associated with the remarkable improvement in pancreatic β-cell morphology. |
| | |
Authors:
|
Atsushi Tajima; Takashi Hirata; Kazuo Taniguchi; Yukiko Kondo; Sota Kato; Masako Saito-Hori; Tsuyoshi Ishimoto; Koji Yamamoto |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-8-18 |
Journal Detail:
|
Title: Life sciences Volume: - ISSN: 1879-0631 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-8-29 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375521 Medline TA: Life Sci Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Inc. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Absence of equilibrative nucleoside transporter 1 in ENT1 knockout mice leads to altered nucleoside ...
Next Document: Lasting first impressions: A conservative bias in automatic filters of the acoustic environment.