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Insulin resistance (IR) is the result of long-lasting positive energy balance and the imbalance between the uptake of energy rich substrates (glucose, lipids) and energy output. The defects in the metabolism of glucose in IR and type 2 diabetes are closely associated with the disturbances in the metabolism of lipids. In this review, we have summarized the evidence indicating that one of the important mechanisms underlying the development of IR is the impaired ability of skeletal muscle to oxidize fatty acids as a consequence of elevated glucose oxidation in the situation of hyperglycemia and hyperinsulinemia and the impaired ability to switch easily between glucose and fat oxidation in response to homeostatic signals. The decreased fat oxidation results into the accumulation of intermediates of fatty acid metabolism that are supposed to interfere with the insulin signaling cascade and in consequence negatively influence the glucose utilization. Pathologically elevated fatty acid concentration in serum is now accepted as an important risk factor leading to IR. Adipose tissue plays a crucial role in the regulation of fatty acid homeostasis. The adipose tissue may be the primary site where the early metabolic disturbances leading to the development of IR take place and the development of IR in other tissues follows. In this review we present recent evidence of mutual interaction between skeletal muscle and adipose tissue in the establishment of IR and type 2 diabetes.

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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.