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.
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 cell-specific 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.
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okuyama
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Kyohara
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tajima
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Kaji
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co., Ltd., Odawara, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Koganei
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co., Ltd., Odawara, Japan ; Department of Nutritional and Life Sciences, Kanagawa Institute of Technology, Atsugi, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004 Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
keywords: Adipose tissue; DPP-4 inhibitor; Insulin resistance; Life span; Pancreatic β cell; Type 2 diabetes