The aim of the study was to determine the contribution of skeletal muscle, adipose tissue and liver to the impaired glucose clearance manifesting itself during the initial phase of OGTT in a non-obese animal model of insulin resistance, hereditary hypertriglyceridemic (HHTg) rats. Glucose utilisation and storage in insulin target tissues in vivo and in vitro after a glucose load (3 g/kg b. wt.) administered intragastrically following overnight fasting was compared in adult male HHTg rats and Wistar normotriglyceridemic controls after short-term (2 wk) high-sucrose (70 % calories as sucrose) feeding period. In comparison with normotriglyceridemic controls, in HHTg rats the glucose administration did not stimulate GLUT4 translocation to the plasma membrane in skeletal muscle and adipose tissue that was associated with decreased glucose utilisation by these tissues in vitro. The acute glucose supply did not result in increased glycogen synthesis in the liver and fatty acid synthesis de novo in adipose tissue. On the contrary, the serum glucose, triglyceride and free fatty acid levels remained elevated. In conclusion, in the tissues of HHTg rats, despite the increased insulinemia, the processes leading toward increased glucose utilisation and processes transforming glucose into storage forms, such as triglycerides in adipose tissue and glycogen in skeletal muscle and liver, did not start within this time interval. The combination of the impaired glucose utilisation and the impaired glucose storage in energy reserves leads to higher glycaemia following glucose load in HHTg rats.

Centre of Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

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