oxytocin and Hypoglycemia

Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies, which are related to the anterior and/or posterior gland and can have an onset in childhood or adulthood. The most common aetiology is a sellar or suprasellar lesion, often an adenoma, which causes hypopituitarism due to tumour mass effects, or the effects of surgery and/or radiation therapy. However, other clinical conditions, such as traumatic brain injury, and autoimmune and inflammatory diseases, can result in hypopituitarism, and there are also genetic causes of hypopituitarism. Furthermore, the use of immune checkpoint inhibitors to treat cancer is increasing the risk of hypopituitarism, with a pattern of hormone defects that is different from the classic patterns and depends on mechanisms that are specific for each drug. Moreover, autoantibody production against the pituitary and hypothalamus has been demonstrated in studies investigating the development or worsening of some cases of hypopituitarism. Finally, evidence suggests that posterior pituitary damage can affect oxytocin secretion. The aim of this Review is to summarize current knowledge on non-classic and emerging causes of hypopituitarism, so as to help clinicians improve early identification, avoid life-threatening events and improve the clinical care and quality of life of patients at risk of hypopituitarism.

Topics: Adenoma; Adrenocorticotropic Hormone; Autoimmune Hypophysitis; Brain Injuries, Traumatic; Dwarfism, Pituitary; Empty Sella Syndrome; Endocrine System Diseases; Genetic Diseases, Inborn; Humans; Hypoglycemia; Hypogonadism; Hypophysitis; Hypopituitarism; Hypothyroidism; Immune Checkpoint Inhibitors; Oxytocin; Pituitary Apoplexy; Pituitary Neoplasms; Subarachnoid Hemorrhage

A survey is given on the regulation of the formation of corticoliberin and of pro-opiomelanocortin and of ACTH, respectively, and on the significance of these compounds. The formation of pro-opiomelanocortin is furthered by corticoliberin, vasopressin, oxytocin and angiotensin II. Receptors for the binding of corticoliberin appear in numerous parts of the central nervous system. In various diseases the content of corticoliberin in the plasma and in certain tissues is changed. The inhibition of the ACTH secretion by glucocorticosteroids takes place via a decrease of the formation of corticoliberin and by a reduction of the equipment of the corticotrophic cells with receptors for its binding. The secretion of corticoliberin and of ACTH, respectively, is increased by loads, by hypoglycaemia, by blood losses, by hypoxia and by infections. In the glucocorticosteroid receptors there are 2 types with different affinity to cortisol and corticosterone.

Topics: Adrenocorticotropic Hormone; Angiotensin II; Corticotropin-Releasing Hormone; Hemorrhage; Humans; Hypoglycemia; Hypoxia; Infections; Oxytocin; Pro-Opiomelanocortin; Receptors, Cell Surface; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Cells, Cultured; Corticotropin-Releasing Hormone; Drug Interactions; Epinephrine; Gonadotropins, Pituitary; Hemodynamics; Humans; Hypoglycemia; Hypothalamo-Hypophyseal System; Hypothalamus; Hypothermia, Induced; Insulin; Neural Pathways; Neurotransmitter Agents; Norepinephrine; Oxytocin; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Rats; Somatostatin; Stress, Physiological

Topics: Adrenocorticotropic Hormone; Calcitonin; Erythropoietin; Gonadotropins; Growth Hormone; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Neoplasms; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Peptides; Placental Lactogen; Prolactin; Radioimmunoassay; Receptors, Cell Surface; Thyrotropin; Vasopressins

In order to establish whether melatonin alters basal and/or stimulated oxytocin secretion, 18 normal men were treated (p.o.) with 6 or 12 mg melatonin or placebo in basal conditions (N-6 subjects) or concomitantly to the administration of insulin (O.15 IU/kg body weight in an i.v. bolus) (N-6 subjects) or angiotensin II (increasing doses of 4, 8 and 16 ng/kg/min, at intervals of 20 min). The administration of 6 or 12 mg melatonin did not change basal and angiotensin II-stimulated oxytocin secretion. In contrast, the oxytocin response to insulin-induced hypoglycemia was significantly reduced by melatonin treatment. In fact, the mean peak oxytocin response to hypoglycemia was 2.2 times higher than baseline in the absence of melatonin, whereas it was 1.6 times higher than basal value after administration of 6 or 12 mg melatonin. These data indicate an involvement of melatonin in the regulation of the oxytocin response to hypoglycemia in normal men. The lack of effects of melatonin on basal and angiotensin II-stimulated oxytocin secretion argues against the possibility that melatonin exerts an overall modulatory role on oxytocin secretion in humans.

Topics: Adult; Angiotensin II; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Melatonin; Oxytocin; Reference Values

In order to establish whether nitric oxide (NO) participates in the regulation of arginine-vasopressin (AVP) and/or oxytocin (OT) secretion in humans, six normal men were treated with placebo (normal saline) or the NO synthase inhibitor N,G-nitro-L-arginine methyl ester (L-NAME), given at doses (40 micrograms kg-1 injected plus 50 micrograms kg-1 infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out both in basal conditions and during stimulation of posterior pituitary secretion with insulin (0.15 IU kg-1)-induced hypoglycaemia. The administration of saline or L-NAME alone was unable to change basal AVP or OT levels. Insulin-induced hypoglycaemia, however, enhanced plasma AVP and OT levels by two-fold in the absence of L-NAME and by four-fold in the presence of the NO synthase inhibitor (NOS). Blood glucose levels decreased in a similar manner during the insulin tolerance tests, regardless of L-NAME administration. In all experiments, AVP and OT responses to hypoglycaemia followed a similar pattern, with mean peak levels at 45 min. These data suggest that in normal men NO is not involved in regulation of basal AVP and OT secretions, whereas it exerts an inhibitory role in the control of the posterior pituitary hormone responses to hypoglycaemia.

Topics: Adult; Amino Acid Oxidoreductases; Arginine; Arginine Vasopressin; Blood Glucose; Glucose Tolerance Test; Humans; Hypoglycemia; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxytocin; Renin

The responses of plasma adrenocorticotrophin (ACTH), cortisol, growth hormone (GH) and prolactin to insulin-induced hypoglycaemia were studied in six lean male subjects (age 22-29 years). Intravenous insulin tests were performed with and without oxytocin infusion. Blood sugar nadir occurred at the onset of symptoms (time S) with no significant differences between oxytocin and saline infusion. During the oxytocin infusion mean plasma oxytocin increased from 1.9 pmol/l to 138 pmol/l. Peak increase in plasma ACTH (oxytocin 266 +/- 54 ng/l; saline 281 +/- 43 ng/l, mean +/- SEM) was at S + 10 min while peak plasma cortisol (oxytocin 680 +/- 47 nmol/l: saline 656 +/- 40 nmol/l) was measured at S +/- 60 min, peak GH (oxytocin 96 +/- 17.8 mU/l; saline 106 +/- 18.6 mU/l) at S + 60 min and prolactin (oxytocin 1332 +/- 239 mU/l; saline 1242 +/- 273 mU/l) at S + 30 min. There were no significant differences in plasma concentrations of ACTH, cortisol, GH or prolactin between saline and oxytocin infusion. The results indicate that oxytocin has no effect on plasma ACTH, cortisol, GH and prolactin responses to insulin-induced hypoglycaemia. In particular they fail to support previous studies which suggested an inhibitory role for oxytocin in ACTH secretion.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Adult; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Oxytocin; Pituitary Gland, Anterior; Prolactin

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Depression, Chemical; Endorphins; Female; Humans; Hydrocortisone; Hypoglycemia; Male; Oxytocin; Somatostatin

The hypothalamic neurochemicals neuropeptide Y (NPY), orexin-A (ORX), and oxytocin (OXY) exert glucoregulatory effects upon intracerebral administration, findings that support their potential function within neural pathways that maintain glucostasis. Current understanding of how these neurotransmitter systems respond to the diabetes mellitus complication, insulin-induced hypoglycemia, is limited to knowledge of neuropeptide gene transcriptional reactivity. We investigated the hypothesis that hypoglycemia elicits hypothalamic site-specific alterations in levels of these neurochemicals, and that adjustments in local neurotransmitter availability may be regulated by catecholaminergic (CA) input from the caudal dorsomedial hindbrain. The arcuate (ARH) and paraventricular (PVH) hypothalamic nuclei and lateral hypothalamic area (LHA) were each microdissected from adult male rats pretreated by caudal fourth ventricular administration of the selective CA neurotoxin, 6-hydroxydopamine (6-OHDA), or vehicle prior to insulin (INS)-induced hypoglycemia. Hypoglycemia stimulated ARH NPY gene expression and NPY accumulation in the ARH and LHA, but not PVH. 6-OHDA pretreatment did not modify the positive NPY mRNA response to INS, but blunted hypoglycemic augmentation of ARH and LHA NPY content while increasing PVH NPY levels in response to hypoglycemia. INS-treated rats exhibited diminished LHA ORX gene expression and increased [ARH; LHA] or decreased [PVH] tissue ORX protein levels. 6-OHDA+INS animals showed a comparable decline in ORX transcripts, but attenuated augmentation of ARH and LHA ORX content and elevated PVH ORX levels. OT mRNA and protein were respectively decreased or unchanged during hypoglycemia, responses that were uninfluenced by hindbrain CA nerve cell destruction. These results illustrate divergent adjustments in glucoregulatory neurotransmitter gene expression and site-specific protein accumulation in the hypothalamus during hypoglycemia. Evidence that 6-OHDA pretreatment does not modify NPY or ORX transcriptional reactivity to hypoglycemia, but alters hypoglycemic patterns of NPY and ORX accretion implicates dorsomedial hindbrain CA neurons in regulation of translation/post-translational processing and site-specific availability of these neurotransmitters in the hypothalamus during hypoglycemia.

Topics: Animals; Blood Glucose; Blotting, Western; Catecholamines; Glucose; Hydroxydopamines; Hypoglycemia; Hypoglycemic Agents; Hypothalamus; Immunohistochemistry; Insulin; Intracellular Signaling Peptides and Proteins; Male; Neuropeptide Y; Neuropeptides; Neurotoxins; Neurotransmitter Agents; Orexins; Oxytocin; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Rhombencephalon; RNA, Messenger; Sympathectomy, Chemical

The present study was undertaken to establish whether oxytocin (OT) is able to modify the NPY response to insulin-induced hypoglycemia in man. At 8:00 AM of 2 different days at least 1 week apart, 10 normal men were tested with insulin (0.15 IU/kg) and with the administration of OT (infused from time -15-60 min, at a constant rate of 2 mIU/ml) or placebo. Plasma NPY concentrations rose significantly during insulin tolerance test (ITT). Oxytocin treatment significantly reduced the NPY response to hypoglycemia. The finding demonstrates for the first time in humans that the systemic administration of OT exerts an inhibitory effect on the NPY rise caused by insulin-induced hypoglycemia.

Topics: Adult; Humans; Hypoglycemia; Insulin; Male; Neuropeptide Y; Oxytocin

Activation of central type II glucocorticoid receptors (GR) during neutral protamine Hagedorn insulin (NPH) administration exacerbates recurring hypoglycemia. The hypothalamic paraventricular nucleus (PVN) integrates metabolic sensory input, controls autonomic and neuroendocrine motor outflow, and is characterized by abundant GR expression. The present studies investigated the hypothesis that PVN GR mediate intensification of hypoglycemia by serial NPH dosing, and that PVN glucokinase (GCK) and glucoregulatory neuropeptide genes acclimate to this treatment paradigm through GR-dependent mechanisms. Groups of adult male rats were injected subcutaneously with one or four doses of NPH, on as many days, while controls received vehicle. Bilateral administration of the selective GR antagonist, CP-472555, into the PVN prior to the first three NPH injections prevented amplification of hypoglycemia in response to the final insulin dose, while intra-PVN delivery of the GR agonist, dexamethasone, to euglycemic rats did not modify ensuing NPH-induced hypoglycemia. Quantitative real-time RT-PCR analysis of microdissected PVN tissue revealed that GCK, corticotropin-releasing hormone (CRH), oxytocin (OT), and vasopressin (VP) mRNA levels were unchanged in response to acute NPH, and baseline gene profiles measured 24 h after antecedent injections were similar to vehicle controls. In contrast, serial dosing with NPH elevated CRH and GCK, diminished OT, but did not alter VP gene transcripts. Intracerebroventricular CP-472555 delivery in conjunction with antecedent NPH dosing prevented transcriptional habituation of GCK and OT genes, but did not modify CRH or VP mRNA profiles. The present data show that activation of PVN GR during antecedent intermediate insulin-induced hypoglycemia is required for exacerbation of recurring hypoglycemia, and receptor stimulation in the absence of hypoglycemia and/or its sequelae does not intensify the effects of subsequent NPH administration. The results also provide evidence for acclimation of PVN CRH, GCK, and OT gene profiles to serial NPH dosing, and demonstrate that GR may be involved in GCK and OT transcriptional adaptation to ongoing intermediate insulin-induced hypoglycemia.

Topics: Animals; Corticotropin-Releasing Hormone; Dexamethasone; Gene Expression Profiling; Gene Expression Regulation; Glucokinase; Hypoglycemia; Injections, Intraventricular; Insulin, Isophane; Male; Neuropeptides; Oxytocin; Paraventricular Hypothalamic Nucleus; Phenanthrenes; Pyridines; Rats; Receptors, Glucocorticoid; RNA, Messenger; Transcriptional Activation; Vasopressins

Both anxiety-related behavior [J.A. Amico, R.C. Mantella, R.R. Vollmer, X. Li, Anxiety and stress responses in female oxytocin deficient mice, J. Neuroendocrinol. 16 (2004) 1-6; R.C. Mantella, R.R. Vollmer, X. Li, J.A. Amico, Female oxytocin-deficient mice display enhanced anxiety-related behavior, Endocrinology 144 (2003) 2291-2296] and the release of corticosterone following a psychogenic stress such as exposure to platform shaker was greater in female [J.A. Amico, R.C. Mantella, R.R. Vollmer, X. Li, Anxiety and stress responses in female oxytocin deficient mice, J. Neuroendocrinol. 16 (2004) 1-6; R.C. Mantella, R.R. Vollmer, L. Rinaman, X. Li, J.A. Amico, Enhanced corticosterone concentrations and attenuated Fos expression in the medial amygdala of female oxytocin knockout mice exposed to psychogenic stress, Am. J. Physiol. Regul. Integr. Comp. Physiol. 287 (2004) R1494-R1504], but not male [R.C. Mantella, R.R. Vollmer, J.A. Amico, Corticosterone release is heightened in food or water deprived oxytocin deficient male mice, Brain Res. 1058 (2005) 56-61], oxytocin gene deletion (OTKO) mice compared to wild type (WT) cohorts. In the present study we exposed OTKO and WT female mice to another psychogenic stress, inserting a rectal probe to record body temperature followed by brief confinement in a metabolic cage, and measured plasma corticosterone following the stress. OTKO mice released more corticosterone than WT mice (P<0.03) following exposure to this stress. In contrast, if OTKO and WT female and male mice were administered insulin-induced hypoglycemia, an acute physical stress, corticosterone release was not different between genotypes. The absence of central OT signaling pathways in female mice heightens the neuroendocrine (e.g., corticosterone) response to psychogenic stress, but not to the physical stress of insulin-induced hypoglycemia.

Topics: Animals; Corticosterone; Female; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Mice; Mice, Knockout; Oxytocin; Stress, Psychological

A limiting factor to the clinical management of diabetes is iatrogenic hypoglycemia. With multiple hypoglycemic episodes, the collective neuroendocrine response that restores euglycemia is impaired. In our animal model of recurrent hypoglycemia (RH), neuroendocrine deficits are accompanied by a decrease in medial hypothalamic activation. Here we tested the hypothesis that the medial hypothalamus may exhibit unique changes in the expression of regulatory proteins in response to RH. We report that expression of the immediate early gene FosB is increased in medial hypothalamic nuclei, anterior hypothalamus, and posterior paraventricular nucleus of the thalamus (THPVN) of the thalamus following RH. We identified the hypothalamic PVN, a key autonomic output site, among the regions expressing FosB. To identify the subtype(s) of neuronal populations that express FosB, we screened candidate neuropeptides of the PVN for coexpression using dual fluorescence immunohistochemistry. Among the neuropeptides analyzed [including oxytocin, vasopressin, thyrotropin-releasing hormone, and corticotropin-releasing factor (CRF)], FosB was only identified in CRF-positive neurons. Inhibitory gamma-aminobutyric acid-positive processes appear to impinge on these FosB-expressing neurons. Finally, we observed a significant decrease in the presynaptic marker synaptophysin within the PVN of RH-treated vs. saline-treated rats, suggesting that rapid alterations of synaptic morphology may occur in association with RH. Collectively, these data suggest that RH stress triggers cellular changes that support synaptic plasticity, in specific neuroanatomical sites, which may contribute to the development of hypoglycemia-associated autonomic failure.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Blotting, Western; Epinephrine; Fluorescent Antibody Technique; gamma-Aminobutyric Acid; Glucagon; Hydrocortisone; Hypoglycemia; Hypothalamus; Hypothalamus, Middle; Immunohistochemistry; Male; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Recurrence; Synaptophysin; Thyrotropin-Releasing Hormone; Vasopressins

Pre-eclampsia is a serious obstetric complication associated with a high rate of maternal and fetal morbidity and mortality. We report the case of a woman with a medical history of insulin-dependent diabetes mellitus and seizures possibly related to hypoglycemia who was admitted for an emergency cesarian due to severe pre-eclampsia and macrosomic fetus. In the first hour after delivery she experienced loss of consciousness and seizure, with vaginal bleeding and hypovolemic shock. Maximum vigilance is required for a patient with several concomitant diseases and a high-risk pregnancy. All prophylactic measures to lower the risk to mother and fetus should be undertaken. We analyze preanesthetic assessment, differential diagnosis, and choice of anesthesia in relation to this case.

Topics: Adult; Cesarean Section; Diabetes Mellitus, Type 1; Diagnosis, Differential; Embolism, Amniotic Fluid; Emergencies; Epilepsy; Female; Fetal Macrosomia; Humans; Hypoglycemia; Hysterectomy; Infant, Newborn; Oxytocin; Postoperative Complications; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy, High-Risk; Puerperal Disorders; Shock; Stroke; Uterine Hemorrhage

The present study was undertaken in order to establish the possible involvement of 5-HT3 serotonergic receptors in the control of basal and/or hypoglycemia-stimulated arginine vasopressin (AVP) and/or oxytocin (OT) secretion. For this purpose, 12 normal men were injected intravenously with a bolus of 4 mg ondansetron, a specific 5-HT3 receptor antagonist, under basal conditions (n = 6) or 30 min before insulin (0.15 IU/kg body weight) administration (n = 6) (insulin tolerance test (ITT)). Control experiments with normal saline instead of ondansetron treatment were performed. Furthermore, on a different occasion, the same subjects were tested in identical experimental conditions with 8 mg ondansetron. Our results showed that the hypoglycemic response to insulin was similar during the ITT and ondansetron plus ITT. Inhibition of 5-HT3 serotonergic receptors with ondansetron (4 or 8 mg) did not modify the basal secretion of AVP and OT and the OT response to insulin-induced hypoglycemia. In contrast, the administration of 4 or 8 mg ondansetron significantly reduced in a similar manner hypoglycemia-induced AVP rise. Mean peak level at 45 min after insulin injection was 2.25 times higher than baseline in the control ITT and 1.5 times higher than basal value in the ondansetron (4 or 8 mg) plus ITT. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to hypoglycemia, without modifying the simultaneous OT response. On the other hand, 5-HT3 receptors do not appear to be involved in the control of basal posterior pituitary hormone secretions.

Topics: Adult; Arginine Vasopressin; Humans; Hypoglycemia; Insulin; Kinetics; Male; Ondansetron; Oxytocin; Placebos; Receptors, Serotonin; Serotonin Antagonists

Arginine-vasopressin (AVP) and oxytocin (OT) secretions are abnormally stimulated by hypoglycaemia in patients with IDDM. Since previous studies showed that AVP secretion is influenced by the persistence of residual endogenous insulin secretion, we wondered whether this factor also regulates OT secretion.. Case-control study: the OT response to insulin-induced hypoglycaemia was measured in normal and diabetic patients with or without residual endogenous insulin secretion.. Ten normal male subjects, 10 C-peptide positive (CpP) and 11 C-peptide negative (CpN) male diabetic patients.. plasma C-peptide levels were measured after intravenous administration of 1 mg glucagon. Insulin tolerance test (ITT): diabetics were studied after optimization of their metabolic status by 3 days of treatment with constant subcutaneous insulin infusion. CpP and CpN diabetics and normal controls were tested with an intravenous administration of 0.15 IU per kg body weight insulin. Blood samples for OT assay were taken just before the rapid injection of insulin (time 0) and at time 15, 30, 45 and 60 min.. The basal concentrations of OT were similar in all groups. Insulin induced a similar hypoglycaemic nadir in all groups at 30 min, even though diabetic groups showed a delayed recovery in blood glucose levels. The glycaemic pattern was similar in all diabetic patients. Hypoglycaemia-induced OT rise was significantly higher in the two diabetic groups than in the normal group. However, CpN patients showed significantly higher OT increments than CpP subjects.. These data indicate that a residual endogenous insulin secretion exerts a partial protective action against the hypothalamic-pituitary disorder affecting the OT secretory system in IDDM.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Glucagon; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Insulin Secretion; Male; Oxytocin

The responses of serum oxytocin (OT) and vasopressin (AVP) to the serotonergic HT1A agonist buspirone (15 mg p.o.) or the HTD1 agonist sumatriptan (6 mg injected subcutaneously) were evaluated in 7 normal men either in basal conditions or during an insulin (0.15 iu/kg as an i.v. bolus) tolerance test (ITT). Neither buspirone nor sumatriptan administration modified the basal secretion of AVP and OT. Stimulation of 5HT-1D receptors with sumatriptan was unable to change neither AVP nor OT response to insulin-induced hypoglycemia. On the other hand, the pretreatment with the 5HT1A agonist buspirone significantly enhanced the OT response during hypoglycemia, without modifying the AVP rise. The results of this study suggest that serotonergic 5HT1A receptors may interact with hypoglycemia in the stimulation of OT, but not AVP secretion.

Topics: Adult; Arginine Vasopressin; Buspirone; Humans; Hypoglycemia; Insulin; Male; Oxytocin; Pituitary Hormones, Posterior; Receptors, Serotonin; Serotonin Receptor Agonists; Sumatriptan

Previous studies have demonstrated that the nitric oxide (NO) synthase inhibitor L-NAME exerts positive effects on the arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia, suggesting inhibitory actions of NO. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in regulation of NO action. AVP and OT secretory patterns during insulin (0.15 IU/kg, i.v.)-tolerance tests (ITT) were examined in seven normal male subjects with (experimental tests) and without (control test) concomitant treatment with L-NAME (40 micrograms/kg injected plus 50 micrograms/kg infused, i.v.), the GABAergic agent sodium valproate (600 mg in three divided doses orally) or the combination of L-NAME and sodium valproate. Insulin-induced hypoglycemia increased by 2-fold (peak vs. baseline) plasma AVP and OT levels. In the presence of L-NAME, plasma AVP and OT levels rose 3-fold in response to hypoglycemia and were significantly higher than those in the control test. Administration of sodium valproate alone changed neither AVP nor OT secretory patterns during ITT. In contrast, sodium valproate abolished the facilitating effect of L-NAME on both AVP and OT responses to hypoglycemia. In the ITT plus L-NAME plus sodium valproate test, plasma AVP and OT levels were not significantly different at any time point from those observed during the control ITT. These data indicate a GABAergic mediation of the inhibitory modulation by NO of the AVP and OT responses to insulin-induced hypoglycemia.

Topics: Adult; Arginine Vasopressin; Blood Glucose; Enzyme Inhibitors; GABA Agents; gamma-Aminobutyric Acid; Humans; Hypoglycemia; Insulin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxytocin; Valproic Acid

The neurohypophysial peptide oxytocin (OT) is released in response to different stressors and has been suggested as a 'stress hormone'. In addition, we have recently shown that centrally administered histamine (HA), which is a mediator of stress-induced release of ACTH and prolactin (PRL), stimulates OT secretion. The aim of the present investigation was to further characterize the HA-induced OT secretion with respect to the type of postsynaptic receptor involved and to investigate the possible role of OT in HA- and stress-induced ACTH and PRL secretion. We studied (1) the effect of HA, HA agonists and HA antagonists on OT secretion in normal male rats, (2) the secretion of OT in response to HA stimulation and to restraint stress, endotoxin stress [lipopolysaccharide (LPS) administration] and insulin/hypoglycemia stress and compared the OT response to that of arginine vasopressin (AVP), (3) the OT response to restraint stress or HA in normal and AVP-deficient Brattleboro rats (DI) suffering from diabetes insipidus and (4) the effect of inhibiting the oxytocinergic system by immunoneutralization or receptor blockade on HA- and stress-induced ACTH and PRL release in normal as well as in DI rats. HA, an H1 and an H2 receptor agonist, stimulated the OT secretion dose-dependently. The HA-induced release of OT was inhibited by pretreatment with an H1 or an H2 receptor antagonist. Restraint stress and HA but not LPS or insulin stress induced an increase in peripheral OT levels, whereas only LPS stress and HA caused an increase in circulating AVP levels. Neither an OT antiserum nor an OT antagonist inhibited the HA- or restraint-stress-induced ACTH or PRL release in normal rats. AVP-deficient DI rats showed, in comparison with their nondeficit counterparts, an increased basal level of OT and no increase in OT levels following restraint stress, whereas the OT response to HA was similar in the two rat types. In AVP-deficient rats immunoneutralization of OT had no inhibitory effect on the HA- and restraint-stress-induced ACTH and PRL response. The ACTH and PRL response to restraint stress and the ACTH response to HA was impaired in DI rats compared to their healthy controls. We conclude (1) that HA stimulates OT secretion via activation of postsynaptic H1 and H2 receptors, and (2) that, in contrast to AVP, OT does not seem to be involved in HA- and restraint-stress-induced ACTH and PRL secretion.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Dose-Response Relationship, Drug; Histamine; Histamine Agonists; Hypoglycemia; Male; Oxytocin; Prolactin; Rats; Rats, Brattleboro; Rats, Wistar; Restraint, Physical; Stress, Psychological

Colchicine blockade of axonal transport from the paraventricular nucleus to the median eminence was used to indirectly infer hypothalamic ACTH secretagog release in awake rats. Median eminence contents of CRF, arginine vasopressin (AVP) and oxytocin (OT) were determined by RIA after insulin-induced hypoglycemia, restraint, and novelty. Insulin decreased circulating glucose concentrations and increased ACTH and corticosterone values. Median eminence CRF and AVP content declined but OT content did not. Both novelty and restraint stressors increased circulating ACTH and corticosterone concentrations. Secretagog measurements indicated decreases in OT content without concomitant decreases in either CRF or AVP with both stressors. These results indicate that: 1) colchicine blockade of axonal transport is useful in studying patterns of secretagog release in animals undergoing psychological stressors; 2) in contrast to physical stressors, OT appears to be a major component of the hypothalamic-pituitary-adrenal response to psychological stress; 3) the patterns of secretagog release differ with regards to physical and psychological stressors.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Axonal Transport; Colchicine; Corticosterone; Corticotropin-Releasing Hormone; Hypoglycemia; Hypothalamus; Insulin; Male; Median Eminence; Oxytocin; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stress, Physiological

Arginine vasopressin (AVP) and oxytocin (OT) responses during an insulin (0.15 IU/kg body weight) tolerance test (ITT) were evaluated in normal men while they were infused with normal saline, glucose or fructose. Insulin-induced hypoglycemia produced significant plasma AVP and OT increments in the control test. The infusion of fructose was unable to change the posterior pituitary hormonal responses to hypoglycemia. In contrast, AVP and OT responses during ITT were completely abolished when the concomitant infusion of glucose prevented insulin-induced hypoglycemia. These data exclude a direct role of hyperinsulinemia in the mechanism underlying the AVP and OT responses during ITT. Furthermore, since glucose, but not fructose, crosses the blood-brain barrier (BBB), the posterior pituitary hormone responses to hypoglycemia appear to be generated by stimulations of glucosensitive areas located inside the BBB.

Topics: Adult; Arginine Vasopressin; Blood-Brain Barrier; Fructose; Glucose; Humans; Hypoglycemia; Insulin; Male; Oxytocin; Receptors, Cell Surface; Reference Values

Glucocorticoids are known to reduce both ACTH and arginine vasopressin responses to insulin-induced hypoglycemia in normal men. The present study was undertaken in order to establish whether glucocorticoids are capable of modifying the oxytocin (OT) response to hypoglycemia. For this purpose, 8 normal men (28-33 yr) were tested with insulin (0.15 IU/kg in an iv bolus) [insulin tolerance test (ITT)] with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin). Eight different subjects (29-35 yr) were tested with dexamethasone alone. The administration of dexamethasone (2 or 4 mg) alone changed neither ACTH nor OT concentrations in the plasma during the next hour. Insulin produced similar hypoglycemic responses, regardless of dexamethasone treatment. ACTH levels rose significantly in response to insulin-induced hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs baseline). Two and four mg dexamethasone produced similar significant reductions of the ACTH response to hypoglycemia (p less than 0.02 at 45 min, p less than 0.05 at 30 and 60 min vs ITT). In the ITT, OT levels rose significantly in response to hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs basal value). The pretreatment with 2 or 4 mg dexamethasone reduced in a similar manner the hypoglycemia-induced OT rise (p less than 0.05 at 30 and 45 min vs ITT). These findings show a partial inhibition by dexamethasone of the OT response to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Dexamethasone; Humans; Hypoglycemia; Insulin; Kinetics; Male; Oxytocin

Oxytocin has been shown to influence insulin, glucagon and blood glucose levels in various experimental situations. The present study was performed in order to obtain support for a possible interaction of glucose and oxytocin under physiological conditions. We therefore studied whether or not short-term food deprivation (24 hours) affects basal oxytocin levels in male, female and lactating rats, since this is a situation when glucose is mobilized to prevent hypoglycaemia. Secondly, we studied whether oxytocin levels rise in a situation when blood glucose levels fall, i.e. following i.p. injection of insulin (20 U kg-1). In order to explore the role of oxytocin more directly, we investigated whether i.p. injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin affects blood glucose levels. Plasma levels of oxytocin, insulin and glucagon were measured with radioimmunoassay in samples obtained after decapitation. We found that oxytocin levels were significantly increased following short-term food deprivation in lactating rats. We also found that insulin-induced hypoglycaemia could elevate plasma levels of oxytocin in female and male rats. In addition, administration of an oxytocin antagonist cause a small, but significant decrease in blood glucose levels after 30 min. These data imply that oxytocin may be one of several factors that take part in the control of blood glucose regulation.

Topics: Animals; Blood Glucose; Female; Food Deprivation; Hypoglycemia; Male; Oxytocin; Rats; Rats, Inbred Strains; Vasotocin

Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of alpha-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg i.v. insulin under control conditions, and during non-selective alpha-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6 +/- 0.8 pmol/l (mean +/- SEM) basally to a maximum of 2.5 +/- 0.8 pmol/l following hypoglycemia (p less than 0.05). An exaggerated response was found during phentolamine blockade, with a maximum plasma vasopressin of 11.5 +/- 0.4 pmol/l (by analysis of variance, p less than 0.05). The plasma oxytocin response to hypoglycemia was similarly increased during phentolamine compared to control. Plasma growth hormone rose to 94 +/- 19 mU/l, and during blockade with phentolamine the response was significantly reduced reaching a peak of 34 +/- 7 mU/l (by analysis of variance, p less than 0.05). ACTH and prolactin both increased in response to hypoglycemia, but the increases were not affected by phentolamine. An alpha-adrenergic mechanism appears to inhibit the release of arginine vasopressin and oxytocin in response to hypoglycemia, but does not appear to affect the secretion of ACTH.

Topics: Adrenergic alpha-Antagonists; Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Humans; Hypoglycemia; Insulin; Male; Oxytocin; Phentolamine

Gastric acid output was examined following oxytocin injection into the hypothalamic paraventricular nucleus (PVN) or into the vagus nucleus (X) of the medulla in rats with insulin-hypoglycemia. Gastric acid output was reduced following the injection of nanomolar quantities of oxytocin into these nuclei, and the response was dose-dependent. It was also noted that there was a synergistic action on the response by the peptide between PVN and X. The acid response was blocked by section of the vagus nerve at the subdiaphragmatic level or by prior administration of atropine sulfate. These observations suggest that oxytocin in the PVN is active in suppressing gastric acid secretion, and the vagal response is characteristic of activation of the PVN and X.

Topics: Animals; Gastric Acid; Hypoglycemia; Insulin; Male; Medulla Oblongata; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains

The present study was performed in order to establish whether angiotensin II (ANG II) and/or insulin-induced hypoglycemia exert their oxytocin (OT)-releasing effects by interacting with a GABAergic pathway. For this purpose, in 14 normal men the OT responses to ANG II (infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg.min, each dose for 20 min; n = 7) or to insulin (0.15 IU/kg)-induced hypoglycemia (n = 7) were evaluated with or without previous treatment with the GABAergic agonist sodium valproate (600 mg in 3 divided doses, p.o.). In all subjects insulin produced a similar hypoglycemic response regardless of sodium valproate administration. Both ANG II and insulin-induced hypoglycemia produced significant increases in plasma OT levels (mean peaks were about 60% higher than baseline). The pretreatment with sodium valproate was unable to change the OT response to hypoglycemia, whereas it abolished the ANG-II-induced OT rise. These data suggest that in man a GABAergic mechanism is involved in the regulation of the OT response to ANG II, but not in the mediation of poglycemia-induced OT release.

Topics: Adult; Angiotensin II; Blood Glucose; Humans; Hypoglycemia; Insulin; Male; Oxytocin; Valproic Acid

Chronically hyponatremic rats were subjected to various stressors in order to evaluate the possible contribution of magnocellular neurons to the regulation of ACTH secretion, since such rats have markedly inhibited secretion and synthesis of magnocellular arginine vasopressin (AVP) and oxytocin (OT). Stress caused by a novel environment or by insulin-induced hypoglycemia resulted in moderate increases in plasma ACTH, which were of similar magnitude in both hyponatremic and normonatremic rats, and these stressors caused no increase in plasma AVP and OT levels in either group of rats. However, when exposed to ether, hyponatremic rats exhibited a significantly blunted ACTH response compared to normonatremic controls (331 +/- 49 vs. 740 +/- 124 pg/ml; P less than 0.01, respectively), and plasma AVP levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. Intravenous infusion of 2 M NaCl also caused an ACTH release in hyponatremic rats that was significantly smaller than that in their normonatremic counterparts (228 +/- 52 vs. 479 +/- 85 pg/ml; P less than 0.05, respectively), and in this case both plasma AVP and OT levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. However, hyponatremic rats exhibited greatly increased plasma ACTH levels 2 and 96 h after adrenalectomy (ADX), which were statistically equivalent to the increases in ACTH levels in normonatremic rats after ADX. Seven days after ADX parvocellular neurons of the paraventricular nucleus showed strongly increased CRF-41 and AVP-neurophysin, but not OT-neurophysin, immunoreactivities in both normonatremic and hyponatremic rats. These results show that parvocellular CRF-41/AVP-producing neurons in the paraventricular nucleus are not inhibited by chronic hyponatremia, in contrast to magnocellular neurons, and suggest that ACTH secretion induced by ether or hypertonic saline, but not by novel environment or insulin-induced hypoglycemia, is partially mediated by magnocellular AVP and/or OT.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Ether; Hypoglycemia; Hyponatremia; Male; Neurons; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains; Reference Values; Saline Solution, Hypertonic; Stress, Physiological

Plasma oxytocin (OT) levels were measured before and after stimulation with estrogens (1 mg ethynylestradiol orally) or with insulin (0.15 IU/kg)-induced hypoglycemia in seven underweight women with anorexia nervosa, eight normal weight bulimic women, and nine normal controls. Anorectic patients were amenorrhoic; they were tested at their first hospitalization (first tests) and again 8 to 9 weeks later (second tests) when they were eating normally, but were still at a low weight. In addition, anorectic women were tested 16 to 17 weeks after the first test (third tests), when their weight was restored to normal. Normal and bulimic women were tested on the fourth days of normal menstrual cycles. Insulin induced similar hypoglycemic responses in all groups. At each time point of the estrogen tests, plasma estrogen levels were similar in bulimic and normal women, whereas they were significantly lower in anorectic subjects. There were no differences in the basal levels of OT among groups. Both insulin-induced hypoglycemia and estrogen treatment produced striking OT increments in bulimic and control women, without significant differences between groups. During the first tests, no significant increase in plasma OT levels was observed in underweight anorectic women in response to both releasing stimuli. After partial weight recovery, the anorectic women showed a slight, but significant, increase in the OT responses to both insulin-induced hypoglycemia and estrogen administration. Both hypoglycemia- and estrogen-induced OT increases observed during the second tests were significantly lower in underweight anorectic patients than in normal controls. Anorectic subjects regained normal OT responsiveness to both stimuli after complete weight recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anorexia Nervosa; Bulimia; Estrogens; Female; Humans; Hypoglycemia; Insulin; Oxytocin

In animals, there is sexual dimorphism of both neurohypophysial peptide secretion in response to stressful stimuli and to the inhibitory effects of opioids. In men, endogenous opioids inhibit the release of oxytocin when AVP secretion is stimulated by insulin-induced hypoglycemia. We have now investigated the role of endogenous opioids in the AVP and oxytocin response to insulin-induced hypoglycemia in women. Twelve subjects, 6 in the follicular and 6 in the luteal phase of the menstrual cycle, were infused on 2 occasions with naloxone (4 mg bolus and 6 mg/h) or saline. Soluble insulin (Human Actrapid, 0.15 mu/kg, iv) was given and serial blood samples taken. Blood sugar fell significantly (p less than 0.05) and similarly in all groups. In the follicular phase hypoglycemia led to a rise in plasma AVP from 1.3 +/- 0.2 to 1.8 +/- 0.2 pmol/l in the saline-infused subjects (NS), and from 1.0 +/- 0.1 to 2.0 +/- 0.2 pmol/l in the naloxone-infused (p less than 0.05). AVP rose similarly from 0.6 +/- 0.1 to 1.6 +/- 0.5 pmol/l (p less than 0.05) in the luteal phase controls and from 0.8 +/- 0.1 to 1.5 +/- 0.3 pmol/l (p less than 0.05) in naloxone-infused subjects in the luteal phase. There were no significant differences between any of these groups. There were no significant changes in plasma oxytocin in any group. We therefore conclude that in women, unlike men, endogenous opioids do not modulate oxytocin or vasopressin release during insulin-induced hypoglycemia.

Topics: Arginine Vasopressin; Endorphins; Female; Follicular Phase; Humans; Hypoglycemia; Insulin; Luteal Phase; Naloxone; Oxytocin; Pituitary Gland, Posterior; Sex Factors

The present study was carried out to establish whether the low arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia observed in obese men was due to alteration of the opioid control of posterior pituitary function. For this purpose, the AVP and OT releasing effect of insulin (0.15 IU/kg bw)--induced hypoglycemia was tested in eight normal weight men and in 10 age-matched obese subjects, without and with the previous treatment with the specific opioid receptor antagonist naloxone (3 mg in an iv bolus). In a control study, naloxone was given alone to the same subjects. Obese men showed similar basal glucose, AVP and OT levels, which remained unmodified after treatment with naloxone alone. Insulin induced a similar decrement of blood glucose levels in all subjects, with a nadir at 30 min. Plasma levels of AVP and OT rose strikingly in normal and obese subjects with mean peak responses at 30 min for AVP and at 45 min for OT. However, both AVP and OT responses were significantly lower in obese than in control subjects. Pretreatment with naloxone did not modify the AVP and OT responses to hypoglycemia in normal weight subjects, whereas it significantly enhanced both hormonal responses in obese subjects. In the presence of naloxone normal controls and obese subjects showed similar responses of both AVP and OT to hypoglycemia. These data indicate that an abnormal activity of endogenous opioids might account for the hypothalamic posterior pituitary dysfunction, which is responsible for the low AVP and OT responses to insulin-induced hypoglycemia in obesity.

Topics: Adult; Arginine Vasopressin; Blood Pressure; Hematocrit; Humans; Hypoglycemia; Insulin; Male; Naloxone; Obesity; Osmolar Concentration; Oxytocin

The effect of somatostatin (SRIH) on the release of oxytocin (OT) in response to hypoglycemia during insulin tolerance test (ITT) was studied in seven normal men. Subjects were injected intravenously with 0.15 U/kg insulin alone (control test) or together with SRIH (4.1 micrograms/min x 90 min), naloxone (10 mg in an IV bolus), or the combination of the two substances. Plasma OT concentrations rose significantly during ITT; the OT response was significantly reduced by the treatment with SRIH and increased in the presence of naloxone. When both SRIH and naloxone were given, the OT response to hypoglycemia did not differ from that observed in the control test. These findings provide evidence that the effect of hypoglycemia on plasma OT levels is sensitive to the inhibition by SRIH and by naloxone-sensitive endogenous opioids. Because naloxone reversed the inhibiting effects of SRIH, an involvement of opioid peptides in SRIH action might be supposed. Alternatively, SRIH and naloxone-sensitive opioids might produce their inhibiting effects on OT rise in response to hypoglycemia through independent pathways.

Topics: Adult; Drug Interactions; Humans; Hypoglycemia; Insulin; Kinetics; Male; Naloxone; Oxytocin; Somatostatin

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.

Topics: Adolescent; Adult; Arginine Vasopressin; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Oxytocin

The plasma oxytocin response to insulin-induced hypoglycemia was evaluated in 20 normal male subjects in the basal state (insulin tolerance test (ITT) alone) and after pretreatment with the muscarinic antagonist pirenzepine (40 mg IV 10 min before the ITT in six subjects), the nicotinic antagonist trimethaphan (0.3 mg/min IV for 30 min before the ITT in six subjects), and the dopaminergic receptor agonist bromocriptine (2.5 mg PO 1 hr before the ITT in eight subjects). The drugs did not modify arterial blood pressure nor produce side effects capable of altering oxytocin secretion. Neither pirenzepine nor trimethaphan administration changed the oxytocin response to hypoglycemia, whereas bromocriptine significantly reduced the oxytocin increase during the ITT. These data suggest the involvement of dopaminergic, but not of cholinergic, muscarinic or nicotinic, receptors in the oxytocin response to hypoglycemia.

Topics: Adult; Blood Glucose; Bromocriptine; Humans; Hypoglycemia; Insulin; Insulin, Regular, Pork; Male; Oxytocin; Pirenzepine; Pituitary Gland, Posterior; Receptors, Cholinergic; Receptors, Dopamine; Receptors, Muscarinic; Receptors, Nicotinic; Trimethaphan

We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulin-induced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P less than 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Saline-infused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 +/- 0.4 pmol/l before insulin to 3.2 +/- 1.3 pmol/l at 45 min (P less than 0.05). We conclude that there is opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.

Topics: Adult; Arginine Vasopressin; Humans; Hypoglycemia; Insulin; Male; Naloxone; Oxytocin; Receptors, Opioid

The response of plasma oxytocin to an iv bolus injection of crystalline insulin (0.15 U/kg) was evaluated in 14 normal weight [mean body mass index (BMI) = 23] and in 9 obese (mean BMI = 42) men. Similar blood glucose decrements after insulin injection were observed in the two groups. Obese and normal weight subjects presented similar basal oxytocin levels. In both groups, oxytocin rose significantly during the insulin tolerance test (ITT); however, the peak oxytocin response in the obese men was significantly lower than in the normal weight subjects. Obese men were restudied after substantial weight loss. Basal oxytocin levels and glucose response to insulin did not change after weight reduction. The oxytocin response to the ITT was significantly higher than before slimming and did not differ from that observed in the normal weight subjects. A significant negative correlation between BMI values and oxytocin peak levels during ITT was observed in the lean controls and obese subjects (r = 0.516, p less than 0.02). These results demonstrate that in obese subjects the oxytocin secretory response during an insulin tolerance test is reduced, suggesting the existence of a hypothalamic-pituitary disorder in obesity.

Topics: Adult; Antibodies; Blood Glucose; Body Weight; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Male; Obesity; Oxytocin; Radioimmunoassay; Time Factors

The changes in blood glucose, plasma oxytocin, plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, haematocrit and blood pressure were measured in response to acute insulin-induced hypoglycaemia in six normal male subjects. After the i.v. administration of insulin (0.15 U/kg), plasma concentrations of oxytocin and vasopressin increased rapidly in all subjects and were maximal 15 min after the acute hypoglycaemic reaction (R). Haematocrit increased at the time of the hypoglycaemic reaction, but there was no change in serum osmolality. Systolic blood pressure rose and diastolic blood pressure fell, but mean arterial blood pressure remained unchanged. No changes were demonstrated in plasma concentrations of atrial natriuretic peptide. The release of oxytocin and vasopressin in response to acute hypoglycaemia in man is probably caused by stimulation of the posterior pituitary gland via hypothalamic activation, and not by stimulation of osmoreceptors or baroreceptors.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Hematocrit; Humans; Hypoglycemia; Insulin; Male; Osmolar Concentration; Oxytocin

Oxytocin has been suggested to have behavioral effects opposite to those of vasopressin, and exogenous vasopressin is known to induce ACTH release in man. Thus, we tested the influence of exogenous oxytocin on blood levels of ACTH and cortisol during insulin-induced hypoglycemia and after vasopressin injection. Our results demonstrate an inhibitory effect of exogenous oxytocin on ACTH release and support the hypothesis of a reciprocal, balanced modulation of behavioral and neuroendocrine function by the two closely related neurohormones, vasopressin and oxytocin.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Oxytocin

Topics: Adult; Blood; Cesarean Section; Extraction, Obstetrical; Female; Fetal Death; Fetal Diseases; Glucose; Humans; Hydrogen-Ion Concentration; Hypertension; Hypoglycemia; Infant Mortality; Infant, Newborn; Labor, Obstetric; Monitoring, Physiologic; Natural Childbirth; Oxytocin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Tachycardia

Topics: Blood Glucose; Growth Hormone; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Oxytocin

Topics: Animals; Dogs; Glucose; Hyperglycemia; Hypoglycemia; Insulin; Lipid Metabolism; Metabolism; Oxytocin; Peptides; Rabbits; Vasopressins

Topics: Adult; Blood Glucose; Female; Humans; Hypoglycemia; Injections, Intravenous; Oxytocin; Postpartum Period; Pregnancy; Time Factors

Topics: Circadian Rhythm; Diet Therapy; Female; Humans; Hyperinsulinism; Hypoglycemia; Male; Multiple Sclerosis; Narcolepsy; Oxytocin

Topics: Biomedical Research; Blood Glucose; Castration; Dogs; Fatty Acids; Gonads; Hypoglycemia; Lipids; Menopause; Metabolism; Oxytocin; Pharmacology; Physiology; Research; Sex