A high-fat and fructose diet in dogs mirrors insulin resistance and β-cell dysfunction characteristic of impaired glucose tolerance in humans.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Insulin Resistance* ; Glucose Intolerance* ; Diabetes Mellitus, Type 2*; Humans ; Dogs ; Animals ; Fructose ; Insulin/metabolism ; Diet, High-Fat/adverse effects ; Blood Glucose/metabolism
    • Abstract:
      This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell's capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.
      Competing Interests: Justin Gregory has served as an advisory board member for Sanofi, Eli Lilly, Medtronic, Dompe, vTv Therapeutics, and Mannkind Corporation and in data and safety monitoring roles for vTv Therapeutics and Medtronic. Alan Cherrington is a scientific advisor, consultant, and holds stock in Fractyl Laboratories. He also holds stock in Metavention. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
      (Copyright: © 2023 Gregory et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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    • Grant Information:
      K23 DK123392 United States DK NIDDK NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; R01 DK018243 United States DK NIDDK NIH HHS
    • Accession Number:
      30237-26-4 (Fructose)
      0 (Insulin)
      0 (Blood Glucose)
    • Publication Date:
      Date Created: 20231222 Date Completed: 20231225 Latest Revision: 20240210
    • Publication Date:
      20240210
    • Accession Number:
      PMC10745172
    • Accession Number:
      10.1371/journal.pone.0296400
    • Accession Number:
      38134122