Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus.
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.
Piroli
Gerardo G
GG
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Grillo
Claudia A
CA
Reznikov
Leah R
LR
Adams
Sheila
S
McEwen
Bruce S
BS
Charron
Maureen J
MJ
Reagan
Lawrence P
LP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D051275:Glucose Transporter Type 4; D007328:Insulin; C495694:Slc2a4 protein, rat; D011972:Receptor, Insulin; D005947:Glucose; D003345:Corticosterone