Hindbrain cytoglucopenia-induced increases in systemic blood glucose levels by 2-deoxyglucose depend on intact astrocytes and adenosine release.
The hindbrain contains critical neurocircuitry responsible for generating defensive physiological responses to hypoglycemia. This counter-regulatory response (CRR) is evoked by local hindbrain cytoglucopenia that causes an autonomically mediated increase in blood glucose, feeding behavior, and accelerated digestion; that is, actions that restore glucose homeostasis. Recent reports suggest that CRR may be initially triggered by astrocytes in the hindbrain. The present studies in thiobutabarbital-anesthetized rats show that exposure of the fourth ventricle (4V) to 2-deoxyglucose (2DG; 15 μmol) produced a 35% increase in circulating glucose relative to baseline levels. While the 4V application of the astrocytic signal blocker, fluorocitrate (FC; 5 nmol), alone, had no effect on blood glucose levels, 2DG-induced increases in glucose were blocked by 4V FC. The 4V effect of 2DG to increase glycemia was also blocked by the pretreatment with caffeine (nonselective adenosine antagonist) or a potent adenosine A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine; DPCPX) but not the NMDA antagonist (MK-801). These results suggest that CNS detection of glucopenia is mediated by astrocytes and that astrocytic release of adenosine that occurs after hypoglycemia may cause the activation of downstream neural circuits that drive CRR.
Autonomic Neurosciences Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and.
Richard C
RC
Rogers
Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington.
Sue
S
Ritter
Autonomic Neurosciences Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; and gerlinda.hermann@pbrc.edu.
Gerlinda E
GE
Hermann
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000008:administration & dosage*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007003:Hypoglycemia / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012249:Rhombencephalon / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D001786:Blood Glucose; D003847:Deoxyglucose; D000241:Adenosine
astrocyte; counter-regulation; gliotransmission; medulla