Dinh TT, Sanders NM, Pedrow C, Ritter S (2001) Selective immunotoxin lesion of spinally projecting norepineprhine and epinephrine (NE/E) neurons impairs the glucagon response to 2-deoxy-d-glucose (2DG). Neuroscience 2001 Abstracts 947.1. Society for Neuroscience, San Diego, CA.
Summary: Previous work has shown that the targeted immunotoxin, anti-dopamine ß-hydroxylase conjugated to saporin (DSAP), can be used to selectively destroy subpopulations of hindbrain NE/E neurons projecting to or through a particular DSAP injection site. Using this approach, we have shown that NE/E neurons projecting to the hypothalamus are required for feeding and glucocorticoid responses to 2DG-induced glucoprivation and those projecting spinally are required for the adrenal medullary response. In this study, we injected DSAP or unconjugated saporin (SAP) control solution into the spinal cord at T2-T4 to investigate the role of the spinally projecting NE/E neurons in glucagon secretion induced by 2DG (250 mg/kg). Controls injected spinally with unconjugated saporin (SAP) had a glucagon response that peaked at 308% of pre-2DG levels, while DSAP-injected rats had a significantly blunted response to 2DG, peaking at 197% of pre-2DG levels. 2DG-induced hyperglycemia also was impaired in the DSAP rats, but not in the SAP rats. Both SAP and DSAP rats had normal feeding and glucocorticoid responses to 2DG. Results suggest that spinally-projecting NE/E neurons participate in the neural control of glucagon secretion under conditions of glucose deficit. In combination with other findings, these results indicate that hindbrain NE/E neurons contribute to four major glucoregulatory responses (increased feeding, and increased secretion of glucagon, glucocorticoids and adrenal medullary epinephrine) through their projections to hypothalamic or spinal cord effector sites.
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