Maintaining euglycemia prevents insulin-induced Fos expression in brain autonomic regulatory circuits.
OBJECTIVE
Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply.


METHODS
Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion (control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry.


RESULTS
The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus (DMV, 26 +/- 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats.


CONCLUSIONS
These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range.
Ao
Yan
Y
Department of Medicine, Division of Digestive Diseases and Brain Research Institute, UCLA, Los Angeles, CA 90073, USA.
Wu
Shuying
S
Go
Vay Liang W
VL
Toy
Natalie
N
Yang
Hong
H
D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D007003:Hypoglycemia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos