Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ellmerer, M; Hamilton-Wessler, M; Kim, SP; Huecking, K; Kirkman, E; Chiu, J; Richey, J; Bergman, RN.
Reduced access to insulin-sensitive tissues in dogs with obesity secondary to increased fat intake.
Diabetes. 2006; 55(6):1769-1775
Doi: 10.2337/db05-1509
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- Führende Autor*innen der Med Uni Graz
- Ellmerer Martin
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- Abstract:
- Physiological hyperinsulinemia provokes hemodynamic actions and augments access of macromolecules to insulin-sensitive tissues. We investigated whether induction of insulin resistance by a hypercaloric high-fat diet has an effect on the extracellular distribution of macromolecules to insulin-sensitive tissues. Male mongrel dogs were randomly selected into two groups: seven dogs were fed an isocaloric control diet ( approximately 3,900 kcal, 35% from fat), and six dogs were fed a hypercaloric high-fat diet ( approximately 5,300 kcal, 54% from fat) for a period of 12 weeks. During hyperinsulinemic-euglycemic clamps, we determined transport parameters and distribution volumes of [(14)C]inulin by applying a three-compartment model to the plasma clearance data of intravenously injected [(14)C]inulin (0.8 microCi/kg). In another study with direct cannulation of the hindlimb skeletal muscle lymphatics, we investigated the effect of physiological hyperinsulinemia on the appearance of intravenously injected [(14)C]inulin in skeletal muscle interstitial fluid and compared the effect of insulin between control and high-fat diet groups. The hypercaloric high-fat diet resulted in significant weight gain (18%; P<0.001) associated with marked increases of subcutaneous (140%; P<0.001) and omental (83%; P<0.001) fat depots, as well as peripheral insulin resistance, measured as a significant reduction of insulin-stimulated glucose uptake during clamps (-35%; P<0.05). Concomitantly, we observed a significant reduction of the peripheral distribution volume of [(14)C]inulin (-26%; P<0.05), whereas the vascular distribution volume and transport and clearance parameters did not change as a cause of the diet. The second study directly confirmed our findings, suggesting a marked reduction of insulin action to stimulate access of macromolecules to insulin-sensitive tissues (control diet 32%, P<0.01; high-fat diet 18%, NS). The present results indicate that access of macromolecules to insulin-sensitive tissues is impaired during diet-induced insulin resistance and suggest that the ability of insulin itself to stimulate tissue access is diminished. We speculate that the observed diet-induced defects in stimulation of tissue perfusion contribute to the development of peripheral insulin resistance.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carbon Radioisotopes -
- Dietary Fats - administration & dosage
- Dogs -
- Glucose - metabolism Glucose - pharmacokinetics
- Glucose Clamp Technique -
- Hindlimb - metabolism
- Hyperinsulinism - chemically induced Hyperinsulinism - metabolism
- Insulin - administration & dosage Insulin - blood Insulin - pharmacokinetics
- Insulin Resistance - physiology
- Magnetic Resonance Imaging -
- Male -
- Muscle, Skeletal - metabolism
- Obesity - metabolism
- Random Allocation -
- Tissue Distribution - drug effects