Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance

• Stacey L. Conarello

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Zhihua Li

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• John Ronan

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Ranabir Sinha Roy

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Lan Zhu

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Guoqiang Jiang

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Franklin Liu

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• John Woods

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Emanuel Zycband

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• David E. Moller

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Nancy A. Thornberry

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

• Bei B. Zhang

  Departments of Metabolic Disorders and Molecular Endocrinology, Comparative Medicine, and Immunology and Inflammation, Merck Research Laboratories, Rahway, NJ 07065

抄録

Dipeptidyl peptidase IV (DP-IV), a member of the prolyl oligopeptidase family of peptidases, is involved in the metabolic inactivation of a glucose-dependent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), and other incretin hormones. Here, we investigated the impact of DP-IV deficiency on body weight control and insulin sensitivity in mice. Whereas WT mice displayed accelerated weight gain and hyperinsulinemia when fed a high-fat diet (HFD), mice lacking the gene encoding DP-IV (DP-IV -/- ) are refractory to the development of obesity and hyperinsulinemia. Pair-feeding and indirect calorimetry studies indicate that reduced food intake and increased energy expenditure accounted for the resistance to HFD-induced obesity in the DP-IV -/- mice. Ablation of DP-IV also is associated with elevated GLP-1 levels and improved metabolic control in these animals, resulting in improved insulin sensitivity, reduced pancreatic islet hypertrophy, and protection against streptozotocin-induced loss of β cell mass and hyperglycemia. Together, these observations suggest that chronic deletion of DP-IV gene has significant impact on body weight control and energy homeostasis, providing validation of DP-IV inhibition as a viable therapeutic option for the treatment of metabolic disorders related to diabetes and obesity.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 100 (11), 6825-6830, 2003-05-14

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1362262944269812224
• NII論文ID: 80015988914
• DOI: 10.1073/pnas.0631828100
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0631828100
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