Meal-induced insulin sensitization in conscious and anaesthetized rat models comparing liquid mixed meal with glucose and sucrose

We have recently shown that meal-induced insulin sensitization (MIS) occurs after feeding and decreases progressively to insignificance after 24hof fasting and is caused by action of a hepatic insulin sensitizing substance (HISS). In order to carry out quantitative studies of MIS, some stan-dardized meal intake is required. Our objective was to establish animal models to be tested in both the conscious and anaesthetized state usingintragastric injection of liquid meals in order to quantify MIS. Insulin sensitivity was assessed before and 90min after the meal using therapid insulin sensitivity test (RIST) which is a transient euglycaemic clamp. Rats tested in the conscious state were instrumented under anaesthesia6–9d prior to testing with catheters in the carotid artery, jugular vein and stomach. Meals, injected into the stomach, consisted of a liquid mixedmeal, sucrose, glucose or water. The glucose sequestration in response to insulin increased by 90% and 61% following the liquid mixed meal(10ml/kg) in conscious and anaesthetized rats, respectively. Glucose, sucrose and water did not effectively activate MIS. MIS was completelyreversed in the conscious model by atropine and completely prevented from developing in the anaesthetized model that had previously undergonehepatic denervation. Gastric administration of a liquid mixed meal but not glucose or sucrose is capable of activating MIS for purposes of mechan-istic studies and quantification of the MIS process. The feeding signal is mediated by the hepatic parasympathetic nerves.HISS: RIST: Insulin sensitivity: Meal: Feeding: Sucrose: Glucose