Increased Thirst and Plasma Arginine Vasopressin Levels during 2-Deoxy-d-glucose-induced Glucoprivation in Humans

Abstract

A B S T R A C T Insulin-induced hypoglycemia by unknown mechanism(s) increases plasma arginine vasopressin (AVP) levels in humans. Mechanisms for increased AVP levels during central nervous system glucoprivation were investigated by administering 20-min i.v. infusions of 2-deoxy-D-glucose (50 mg/kg), a competitive inhibitor of glucose utilization, or normal saline (sham), to 24 normal volunteers. Some of the infusions were administered in combination with neuropharmacological blocking agents (placebo). The behavioral, physiological, metabolic, and hormonal correlates of 2-deoxy-D-glucose (2DG)-induced glucoprivation and AVP secretion were studied in a group (n = 5) pretreated for 1 wk with either mazindol (1 mg per os three times per day), a potent norepinephrine and dopamine-reuptake blocker, or placebo. A second group (n = 5) received either propranolol (3 mg/3 min followed by 80 ,tg/min) or normal saline infusion before and during 2DG administration. With 2DG alone, plasma AVP levels increased from 1.3 + 0.3 pg/ml at base line to a peak of 4.5+1.4 pg/ml at 60 min and remained elevated for 150 min. From 30 to 180 min after 2DG administration, the 2DG-infused volunteers increased their water intake in comparison with shaminfused volunteers. Marked increases in epinephrine and slight increases in norepinephrine were associated with increases in plasma glucose and renin activity and decreases in plasma potassium. Plasma sodium and osmolality increased transiently and mean arterial pressure (MAP) fell. These changes, however, were small and inconstant and could not account for the observed increases in thirst and AVP levels. Pretreatment with mazindol prevented the decrease in MAP and the increase in plasma renin activity (PRA) following 2DG infusions without modifying increased thirst, water intake, or AVP responses to glucoprivation. Pretreatment with propranolol effectively blocked ,3-adrenoreceptors as evidenced by increased MAP and plasma epinephrine, and abolition ofthe RPA increases during 2DG-induced glycoprivation, but did not suppress AVP and thirst responses. A cervical cordsectioned patient lacking descending sympathetic outflow had a potentiated thirst response to 2DG-induced glucoprivation in the absence of increases in sodium, catecholamines, and PRA. Thus 2DG administration activates mechanisms for increased thirst and AVP which are unrelated to changes in peripheral catecholamines, MAP, PRA, and osmolality.

Effects of Acute Metabolic Stress on the Peripheral Vasopressinergic System in Schizophrenia

“…The vasopressin data are consistent with previous preclinical (Baylis and Robertson, 1980b) and clinical (Thompson et al, 1981) secretion following 2DG administration. The lack of a significantly greater absolute vasopressin response in schizophrenic patients and its dissociation from the response of the exaggerated PA axis (Elman et al, 1998) may be related to patients in this study presenting no symptoms of polydipsia and hyponatremia, suggesting that they may not have abnormalities in the stressrelated vasopressinergic function.…”

“…independent of peripheral osmotic and/or haemodynamic changes) hypothalamic stimulus for vasopressin secretion (Baylis and Robertson, 1980a,b;Baylis et al, 1981;Thompson et al, 1981;Chiodera et al, 1992) and (ii) unlike cognitive stressors, it is not associated with performance bias, so that equal 'amounts' of perturbation are induced in both cognitively impaired patients with schizophrenia and healthy control subjects. Although this kind of metabolic stress may be distinct from the environmental stress implicated in exacerbation of psychosis (Jansen and Gispen-de Wied, 2000), it may provide unique information pertaining to general stress and limbic responsiveness.…”

Hypoglycemia-Induced Arginine Vasopressin and Oxytocin Release Is Mediated by Glucoreceptors Located Inside the Blood-Brain Barrier

“…Even though a direct action of insulin at the hypothalamic level has been reported [4][5][6][7], normoglycemic hyperinsuliné mie clamp studies have demonstrated that hyperinsuline mia does not promote vasopressin secretion [8], There fore, the AVP and OT responses during an insulin toler ance test (ITT) are supposed to follow direct stimulation of hypothalamic glucoreceptors [4][5][6][7] elicited by the neuropenic symptomatic stimulus [9][10][11][12]. Recent studies This work was supported in part by a 'Ministcro Pubblica Received: Istruzionc* grant and by Bayer Italiana s.p.a.…”

The 2-Deoxyglucose Test as a Supplement to Fasting for Detection of Childhood Hypoglycemia

“…In more than 100 reported 2DG tests (50 mg/kg) in normal adult subjects, the average increase of plasma glucose has been approximately 90 mg/dl (1,7,13,23,25,36,38,39,40). The lowest increase reported among 18 individual normal adult subjects was 26 mg/dl (23,38,39).…”