Mitigation of the somnolence of insulin-induced hypoglycemia by a vasopressin V1 receptor antagonist in the rhesus monkey.
Insulin-induced hypoglycemia causes somnolence in rhesus monkeys, a phenomenon usually considered an aspecific consequence of neuroglycopenia. Previous observations from our laboratory have raised the possibility that arginine vasopressin (AVP) may also play a role in this decrease in wakefulness. In the present study we tested this hypothesis by inducing hypoglycemia (approximately 40 mg/dl) in ovariectomized rhesus monkeys by intravenous administration of insulin in the presence of continuous intracerebroventricular infusions of the V1 receptor antagonist [deamino-Pen1, O-Me-Tyr2,Arg8]-vasopressin (180 micrograms/60 microliters per h) or of its vehicle alone (artificial cerebrospinal fluid, 60 microliters/h). Wakefulness was assessed by a scoring system by observers blinded to the experimental protocol. The AVP antagonist significantly attenuated the decrease in wakefulness observed in response to insulin-induced hypoglycemia (p < .03) without increasing blood glucose levels. These and previous findings suggest that the somnolence induced by a moderate degree of hypoglycemia may not entirely be the direct consequence of neuroglycopenia and that AVP may, directly or indirectly, be involved.
Chen
M D
MD
Laboratory for Neuroendocrinology, University of Texas-Houston Medical School 77225, USA.
Ordög
T
T
Knobil
E
E
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D007003:Hypoglycemia / Q000139:chemically induced / Q000523:psychology*; D007004:Hypoglycemic Agents; D007276:Injections, Intraventricular; D007328:Insulin; D008253:Macaca mulatta; D010052:Ovariectomy; D011897:Random Allocation; D012894:Sleep Stages / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D001127:Arginine Vasopressin; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-