A High-Fat and Fructose Diet in Dogs Mirrors Insulin Resistance and β-cell Dysfunction Characteristic of Impaired Glucose Tolerance in Humans

Gregory, J. M.; Kraft, G.; Man, C. D.; Slaughter, J. C.; Scott, M. F.; Hastings, J. R.; Edgerton, D.; Moore, M. C.; Cherrington, A. D.

doi:10.1101/2023.10.19.563103

bioRxiv · 10.1101/2023.10.19.563103

A High-Fat and Fructose Diet in Dogs Mirrors Insulin Resistance and β-cell Dysfunction Characteristic of Impaired Glucose Tolerance in Humans

Gregory, J. M.·Kraft, G.·Man, C. D.·Slaughter, J. C.·Scott, M. F.·Hastings, J. R.·Edgerton, D.·Moore, M. C.·Cherrington, A. D.

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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 {beta}-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 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 {beta}-cells 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.

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Gregory, J. M., Kraft, G., Man, C. D., Slaughter, J. C., Scott, M. F., Hastings, J. R., Edgerton, D., Moore, M. C., Cherrington, A. D.. 2023-10-23. A High-Fat and Fructose Diet in Dogs Mirrors Insulin Resistance and β-cell Dysfunction Characteristic of Impaired Glucose Tolerance in Humans. https://doi.org/10.1101/2023.10.19.563103

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