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- Title
DPP-4 inhibition improves early mortality, β cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid.
- Authors
Jun Shirakawa; Tomoko Okuyama; Mayu Kyohara; Eiko Yoshida; Yu Togashi; Kazuki Tajima; Shunsuke Yamazaki; Mitsuyo Kaji; Megumi Koganei; Hajime Sasaki; Yasuo Terauchi
- Abstract
Background: Diabetes therapy that not only lowers glucose levels but also lengthens life spans is required. We previously demonstrated that DPP-4 inhibition ameliorated β cell apoptosis and adipose tissue inflammation in β cellspecific glucokinase haploinsufficient mice fed a diet containing a combination of sucrose and linoleic acid (SL). Methods: In this study, we investigated the effects of DPP-4 inhibition in obese diabetic db/db mice fed an SL diet or a control diet containing sucrose and oleic acid (SO). We also examined the effects of DPP-4 inhibition in IRS-1-deficient mice fed an SL or SO diet as a model of insulin resistance. Results: DPP-4 inhibition efficiently increases the active GLP-1 levels in db/db mice. Unexpectedly, the SL diet, but not the SO diet, markedly increases mortality in the db/db mice. DPP-4 inhibition reduces the early lethality in SL-fed db/db mice. DPP-4 inhibition improves glucose tolerance, β cell function, and adipose tissue inflammation in db/db mice fed either diet. No significant changes in glycemic control or β cell mass were observed in any of the IRS-1-deficient mouse groups. Conclusions: A diet containing a combination of sucrose and linoleic acid causes early lethality in obese diabetic db/ db mice, but not in lean and insulin resistant IRS-1 knockout mice. DPP-4 inhibition has protective effects against the diet-induced lethality in db/db mice.
- Subjects
CLINICAL trials; TYPE 2 diabetes; PEOPLE with diabetes; GLUCOKINASE; OLEIC acid; LINOLEIC acid; HUMAN services; THERAPEUTICS
- Publication
Diabetology & Metabolic Syndrome, 2016, Vol 8, p1
- ISSN
1758-5996
- Publication type
Article
- DOI
10.1186/s13098-016-0138-4