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

Conarello, Stacey L ; Li, Zhihua ; Ronan, John ; Roy, Ranabir Sinha ; Zhu, Lan ; Jiang, Guoqiang ; Liu, Franklin ; Woods, John ; Zycband, Emanuel ; Moller, David E ; Thornberry, Nancy A ; Zhang, Bei B

Proceedings of the National Academy of Sciences of the United States of America, 27 May 2003, Vol.100(11), pp.6825-30 [Peer Reviewed Journal]

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  • Title:
    Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance
  • Author: Conarello, Stacey L ; Li, Zhihua ; Ronan, John ; Roy, Ranabir Sinha ; Zhu, Lan ; Jiang, Guoqiang ; Liu, Franklin ; Woods, John ; Zycband, Emanuel ; Moller, David E ; Thornberry, Nancy A ; Zhang, Bei B
  • Description: 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 beta 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.
  • Is Part Of: Proceedings of the National Academy of Sciences of the United States of America, 27 May 2003, Vol.100(11), pp.6825-30
  • Identifier: ISSN: 0027-8424 ; PMID: 12748388 Version:1
  • Subjects: Genetic Predisposition to Disease ; Insulin Resistance ; Dipeptidyl Peptidase 4 -- Metabolism ; Obesity -- Genetics
  • Language: English
  • Source: MEDLINE/PubMed (U.S. National Library of Medicine)

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