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.
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.
Authors: Eric M Blalock; Richard Grondin; Kuey-chu Chen; Olivier Thibault; Veronique Thibault; Jignesh D Pandya; Amy Dowling; Zhiming Zhang; Patrick Sullivan; Nada M Porter; Philip W Landfield Journal: J Neurosci Date: 2010-04-28 Impact factor: 6.167
Authors: Claudia A Grillo; Gerardo G Piroli; Lorain Junor; Steven P Wilson; David D Mott; Marlene A Wilson; Lawrence P Reagan Journal: Physiol Behav Date: 2011-02-24