Original Article Reduced Access to Insulin-Sensitive Tissues in Dogs With Obesity Secondary to Increased Fat Intake

Physiological hyperinsulinemia provokes hemodynamic ac-tions 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 ran-domly selected into two groups: seven dogs were fed an isocaloric control diet (3,900 kcal, 35 % from fat), and six dogs were fed a hypercaloric high-fat diet (5,300 kcal, 54 % from fat) for a period of 12 weeks. During hyperinsu-linemic-euglycemic clamps, we determined transport pa-rameters and distribution volumes of [14C]inulin by applying a three-compartment model to the plasma clear-ance data of intravenously injected [14C]inulin (0.8 Ci/ kg). In another study with direct cannulation of th