Background: Exposure to stress levels of glucocorticoids produces physiological responses that are characteristic of type 2 diabetes, such as peripheral insulin resistance and impairment in insulin-stimulated trafficking of glucose transporter 4 (GLUT4) in muscle and fat. In the central nervous system, stress produces neuroanatomical and neurochemical changes in the hippocampus that are associated with cognitive impairments. Methods: In view of these observations, the current studies examined the effects of short-term (1 week) exposure of stress levels of glucocorticoids upon insulin receptor (IR) expression and signaling, including GLUT4 translocation, in the rat hippocampus. Results: One week of corticosterone (CORT) treatment produced insulin resistance in response to peripheral glucose challenge. In the hippocampus, IR expression was unchanged in CORT-treated rats as compared with vehicle-treated rats. However, insulin-stimulated phosphorylation of the IR, total Akt levels and total GLUT4 levels were reduced in CORT-treated rats when compared to controls. In addition, insulin-stimulated translocation of hippocampal GLUT4 to the plasma membrane was completely abolished in CORT-treated rats. Conclusions: These results demonstrate that in addition to eliciting peripheral insulin resistance, short-term CORT administration impairs insulin signaling in the rat hippocampus, effects that may contribute to the deleterious consequences of hypercortisolemic/hyperglycemic states observed in type 2 diabetes.

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