Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog. Ader, M., Stefanovski, D., Kim, S. P, Richey, J. M, Ionut, V., Catalano, K. J, Hucking, K., Ellmerer, M., Van Citters, G., Hsu, I. R, Chiu, J. D, Woolcott, O. O, Harrison, L. N, Zheng, D., Lottati, M., Kolka, C. M, Mooradian, V., Dittmann, J., Yae, S., Liu, H., Castro, A. V. B, Kabir, M., & Bergman, R. N 22(5):1238–45, 5, 2014.
Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog. [link]Paper  doi  abstract   bibtex   
OBJECTIVE: Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions. METHODS: Metabolic assessment was performed in healthy dogs (n = 90). Whole-body sensitivity from euglycemic clamps (SICLAMP ) was the primary outcome variable, and was measured independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and glucose-stimulated insulin response was measured from hyperglycemic clamp or IVGTT (n = 86 and 36, respectively). RESULTS: SICLAMP was highly variable (5.9-75.9 dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7 ± 0.3 kg), adiposity varied approximately eight-fold and was inversely correlated with SICLAMP (P < 0.025). SICLAMP was negatively associated with fasting insulin, but most strongly associated with insulin clearance. Clearance was the dominant factor associated with sensitivity (r = 0.53, P < 0.00001), whether calculated from clamp or IVGTT. CONCLUSIONS: These data suggest that insulin clearance contributes substantially to insulin sensitivity, and may be pivotal in understanding the pathogenesis of insulin resistance. We propose the hyperinsulinemia due to reduction in insulin clearance is responsible for insulin resistance secondary to changes in body weight.
@article{Ader-2014-ID23,
  title     = {Hepatic insulin clearance is the primary determinant of insulin sensitivity
               in the normal dog.},
  abstract  = {{OBJECTIVE}: Insulin resistance is a powerful risk factor for Type 2
               diabetes and a constellation of chronic diseases, and is most commonly
               associated with obesity. We examined if factors other than obesity are more
               substantial predictors of insulin sensitivity under baseline, nonstimulated
               conditions. {METHODS}: Metabolic assessment was performed in healthy dogs
               (n = 90). Whole-body sensitivity from euglycemic clamps ({SICLAMP} ) was
               the primary outcome variable, and was measured independently by {IVGTT} (n
               = 36). Adiposity was measured by {MRI} (n = 90), and glucose-stimulated
               insulin response was measured from hyperglycemic clamp or {IVGTT} (n = 86
               and 36, respectively). {RESULTS}: {SICLAMP} was highly variable (5.9-75.9
               dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7
               ± 0.3 kg), adiposity varied approximately eight-fold and was inversely
               correlated with {SICLAMP} (P < 0.025). {SICLAMP} was negatively associated
               with fasting insulin, but most strongly associated with insulin clearance.
               Clearance was the dominant factor associated with sensitivity (r = 0.53, P
               < 0.00001), whether calculated from clamp or {IVGTT}. {CONCLUSIONS}: These
               data suggest that insulin clearance contributes substantially to insulin
               sensitivity, and may be pivotal in understanding the pathogenesis of
               insulin resistance. We propose the hyperinsulinemia due to reduction in
               insulin clearance is responsible for insulin resistance secondary to
               changes in body weight.},
  author    = {Ader, Marilyn and Stefanovski, Darko and Kim, Stella P and Richey, Joyce M
               and Ionut, Viorica and Catalano, Karyn J and Hucking, Katrin and Ellmerer,
               Martin and Van Citters, Gregg and Hsu, Isabel R and Chiu, Jenny D and
               Woolcott, Orison O and Harrison, Lisa N and Zheng, Dan and Lottati, Maya
               and Kolka, Cathryn M and Mooradian, Vahe and Dittmann, Justin and Yae,
               Sophia and Liu, Huiwen and Castro, Ana Valeria B and Kabir, Morvarid and
               Bergman, Richard N},
  volume    = {22},
  number    = {5},
  pages     = {1238--45},
  year      = {2014},
  month     = {5},
  url       = {http://www.pubmed.org/24123967},
  pmcid     = {3969862},
  pmid      = {24123967},
  doi       = {10.1002/oby.20625},
  keywords  = {Animals, Insulin, Insulin Resistance, Liver, Male, Body Weight, Obesity,
               Blood Glucose, Body Composition, Body Mass Index, Diabetes Mellitus, Type
               2, Dogs, Fasting, Glucose Clamp Technique, Hyperinsulinism, Magnetic
               Resonance Imaging},
  file      = {FULLTEXT:pdfs/000/000/000000023.pdf:PDF}
}
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