Adrenalectomized Subjects Research Articles

Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy

Corticosteroids can be synthesized in extra-adrenal tissues but the contribution of this to circulating levels in humans is not known. Previous in vitro studies suggest that the 'hybrid' corticosteroid 18-oxocortisol (18-oxoF) is produced from cortisol by aldosterone synthase. We looked for evidence of extra-adrenal production of this and other corticosteroids in 10 subjects stable on long-term glucocorticoid replacement following bilateral adrenalectomy. In phase 1, patients were maintained on cortisol alone (30 mg/day), in phase 2 dexamethasone (2 mg/day), and in phase 3, both cortisol and dexamethasone. Each phase lasted 3 days. On the last day of each phase, 24-h urine collection was performed for analysis of steroid metabolite excretion [using gas chromatography-mass spectrometry (GCMS)] and plasma aldosterone and renin were measured (by radioimmunoassay). Cortisol metabolite excretion rate [tetrahydrocortisone (THE) + tetrahydrocortisol (THF) + allotetrahydrocortisol (aTHF)] fell from 9169 nmol/24 h in phase 1 to 22 nmol/24 h in phase 2, rising to 6843 nmol/24 h in phase 3. Tetrahydroaldosterone (THAldo) excretion was readily detectable and did not alter significantly between phases (26.5, 23.5 and 28.5 nmol/24 h, respectively; P = 0.474). 18-Hydroxycortisol (18-OHF) excretion was easily detectable in phases 1 and 3 (252.5 and 212 nmol/24 h), falling in phase 2 (12 nmol/24 h). 18-oxoF excretion rates were lower but followed a similar pattern (1.62, 0.085 and 1.785 nmol/24 h in phases 1, 2 and 3, respectively). Significant levels of adrenal steroids are found in adrenalectomized subjects. We speculate that this occurs at extra-adrenal sites or in residual adrenal cortex tissue in an ACTH-independent manner. Our data suggest that aldosterone synthase, acting on cortisol, is the source of 18-oxoF and 18-OHF in these subjects. Further studies of corticosteroid production within adrenalectomized subjects, looking for evidence of adrenal regrowth or residual adrenal tissue, are justified.

Timecourse and corticosterone sensitivity of the brain, pituitary, and serum interleukin-1β protein response to acute stress

Activation of peripheral immune cells leads to increases of interleukin-1β (IL-1β) mRNA, immunoreactivity, and protein levels in brain and pituitary. Furthermore, IL-1β in brain plays a role in mediating many of the behavioral, physiological, and endocrine adjustments induced by immune activation. A similarity between the consequences of immune activation and exposure to stressors has often been noted, but the potential relationship between stress and brain IL-1β has received very little attention. A prior report indicated that exposure to inescapable tailshocks (IS) raised levels of brain IL-1β protein 2 h after IS, but only in adrenalectomized (and basal corticosterone replaced) subjects. The studies reported here explore this issue in more detail. A more careful examination revealed that IL-1β protein levels in hypothalamus were elevated by IS in intact subjects, although adrenalectomy, ADX (with basal corticosterone replacement) exaggerated this effect. IL-1β protein increases were already present immediately after the stress session, both in the hypothalamus and in other brain regions in adrenalectomized subjects, and no longer present 24 h later. Furthermore, IS elevated levels of IL-1β protein in the pituitary, and did so in both intact and adrenalectomized subjects. IS also produced increased blood levels of IL-1β, but only in adrenalectomized subjects. Finally, the administration of corticosterone in an amount that led to blood levels in adrenalectomized subjects that match those produced by IS, inhibited the IS-induced rise in IL-1β in hypothalamus and pituitary, but not in other brain regions or blood.

Blockade of the anxiolytic-like action of ipsapirone and buspirone, but not that of 8-OH-DPAT, by adrenalectomy in male rats.

The effect of the 5-HT1A agonists ipsapirone (5 mg/kg), buspirone (5 mg/kg) and 8-OH-DPAT (0.5 mg/kg) on experimental anxiety was examined in sham-operated, adrenalectomized and adrenally demedullated male rats. The animal model of anxiety used was the defensive burying test. At the doses selected, all 5-HT1A compounds produced an anxiolytic-like action by reducing the burying behavior in both sham-operated and demedullated rats. However, in adrenalectomized subjects, while 8-OH-DPAT still reduced burying behavior, ipsapirone and buspirone lost their action. Data suggest that adrenocortical secretions play a role in the anxiolytic-like actions of buspirone and ipsapirone, but not in those of 8-OH-DPAT. Buspirone and ipsapirone also produced a reduction in burying behavior latency in sham-operated animals that was not observed in adrenalectomized or adrenally demedullated rats. These data suggest that adrenaline may be participating in the action of these compounds on the burying behavior latency. Present findings support possible direct relationships between the stimulation of 5-HT1A receptors and adrenal secretions.

Exposure to Acute Stress Induces Brain Interleukin-1β Protein in the Rat

Peripheral immune stimulation such as that provided by lipopolysaccharide (LPS) has been reported to increase brain levels of IL-1beta mRNA, immunoreactivity, and bioactivity. Stressors produce many of the same neural and endocrine responses as those that follow LPS, but the impact of stressors on brain interleukin-1beta (IL-1beta) has not been systematically explored. An ELISA designed to detect IL-1beta was used to measure levels of IL-1beta protein in rat brain. Brain IL-1beta was explored after exposure to inescapable shock (IS; 100 1.6 mA tail shocks for 5 sec each) and LPS (1 mg/kg) as a positive control. Rats were killed either immediately or 2, 7, 24, or 48 hr after IS. Brains were dissected into hypothalamus, hippocampus, cerebellum, posterior cortex, and nucleus tractus solitarius regions. LPS produced widespread increases in brain IL-1beta, but IS did not. Adrenal glucocorticoids are known to suppress IL-1beta production in both the periphery and brain. Thus, it was possible that the stressor did provide stimulus input to the brain IL-1beta system(s), but that the production of IL-1beta protein was suppressed by the rapid and prolonged high levels of glucocorticoids produced by IS. To test this possibility rats were adrenalectomized or given sham surgery, with half of the adrenalectomized rats receiving corticosterone replacement to maintain basal corticosterone levels. IS produced large increases in brain IL-1beta protein in the adrenalectomized subjects 2 hr after stress, whether basal corticosterone levels had been maintained. Thus elimination of the stress-induced rise in corticosterone unmasked a robust and widespread increase in brain IL-1beta.

Circulating adrenaline is not involved in the circadian blood pressure profile

Circadian changes in blood pressure are paralleled by analogous circadian changes in plasma catecholamines: blood pressure, plasma noradrenaline and adrenaline fall at night. To determine whether adrenaline is a prerequisite for the nocturnal fall in blood pressure, the circadian blood pressure profile was studied in adrenalectomized subjects, lacking circulating adrenaline. Ten adrenalectomized subjects and 10 healthy age-matched normotensive controls underwent 24-h non-invasive ambulatory blood pressure monitoring with the Oxford Medilog device. Measurements were taken every 15 min from 7.00 a.m. until 11.59 p.m and every 30 min from 12 midnight until 6.59 a.m. The nocturnal blood pressure fall was calculated for each subject. Mean +/- SD systolic blood pressure decreased at night by 13.2 +/- 9.5 mmHg in the adrenalectomized and by 11.7 +/- 7.3 mmHg (NS) in the control subjects. There was no significant difference between groups in the nocturnal diastolic blood pressure fall (14.4 +/- 5.1 and 13.1 +/- 5.2 mmHg, respectively). Systolic blood pressure decreased by > 10 mmHg in five of the adrenalectomized and eight of the control subjects. Diastolic blood pressure decreased by > 10 mmHg in eight of the adrenalectomized and eight of the control subjects. The normal nocturnal fall in blood pressure in adrenalectomized subjects indicates that circulating adrenaline is not required for a normal circadian blood pressure rhythm.

Ultradian variations of chromogranin A in humans

Chromogranin A (CgA) is an acidic soluble protein exocytotically released from virtually all neuroendocrine secretory vesicles. Here we examined spontaneous variations in CgA and catecholamine concentrations in humans. In normal subjects, basal CgA showed no day-to-day, week-to-week, or diurnal variability. Plasma CgA had significant ultradian variation in normotensives and hypertensives, and in bilaterally adrenalectomized subjects. Gender, but not age or blood pressure, influenced CgA variations, males having fewer (P less than 0.05) peaks per 8 h. Plasma catecholamines had significant ultradian variations in both controls and bilaterally adrenalectomized subjects. Within individuals, neither basal nor peak plasma CgA correlated with catecholamines, nor was there concordance between plasma CgA and catecholamine peaks. Somatostatin, a widespread inhibitor of nonsympathoadrenal neuroendocrine secretion, diminished both the frequency and amplitude of plasma CgA peaks. Thus spontaneous variations in basal CgA are not directly linked to alterations in sympathoadrenal catecholamine secretion. Furthermore, neuroendocrine secretion at sites other than the sympathoadrenal system contributes to spontaneous variations in CgA concentration.

Sympathetic outflow in human muscle nerves increases during hypoglycemia.

The normal response to insulin-induced hypoglycemia bears many characteristics of activation of the sympathetic nervous system. In this study, the impulse pattern of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis was identified by microneurography in the peroneal nerve of seven healthy and two adrenalectomized subjects. After recordings at rest and an intravenous injection of 0.15 IU insulin/kg body wt (0.10 IU insulin/kg body wt in adrenalectomized subjects), MSA was followed for 90 min. Nadir of hypoglycemia (2.0 +/- 0.1 mM) was reached at 30 min. All subjects, including the two adrenalectomized subjects, exhibited an increase of MSA, which peaked at the glucose nadir. The time course of MSA increase was a mirror image of the blood glucose curve. This directly measured increase of MSA may be part of the hemodynamic adjustment to the fall in plasma volume known to occur in hypoglycemia. Another possible cause is direct stimulation of central sympathetic motoneurons.

Effect of CRF on the release of anterior pituitary hormones in normal subjects and patients with Cushing's disease

Patterning of plasma ACTH, beta-EP/beta-LPH and cortisol in response to ovine CRF (1 microgram/kg b.w.t. injected i.v.), was studied in three normal subjects and in five patients with Cushing's disease, two of whom had undergone total bilateral adrenalectomy. CRF caused in all subjects a prompt and concurrent rise of plasma hormone levels. The hormonal response was of the same magnitude in normal controls and in the three untreated Cushing's patients, but was much greater in the two adrenalectomized subjects. No changes were noted, after CRF, in plasma levels of GH, PRL, TSH, LH and FSH. These findings indicate that CRF specifically promotes the pituitary release of ACTH and ACTH-related peptides both in normal subjects and patients with Cushing's disease. In view of the likely CRF hypersecretion of the adrenalectomized patients, their ACTH and beta-EP/beta-LPH hyperresponsiveness to exogenous CRF would denote that the peptide does not down regulate its own pituitary receptors.

Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion.

The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.

The relation between catecholamines, glucagon and pancreatic polypeptide during hypoglycaemia in man

The effects of insulin hypoglycaemia (0.15 IU/kg) on plasma adrenaline, noradrenaline, dopamine, glucagon and pancreatic polypeptide (PP) concentrations were investigated in 6 adrenalectomized subjects and 6 healthy controls. Both the rise in mean plasma insulin and the fall in mean blood glucose concentration were closely similar in the two groups. Mean plasma adrenaline concentration rose by about 3 nmol/l in the normal subjects, but remained unchanged in adrenalectomized subjects. Mean plasma noradrenaline concentration increased by about 2 nmol/l in both groups. Despite the large difference in adrenaline concentrations during hypoglycaemia, there was no significant difference between the responses of the endocrine pancreas of the normal and adrenalectomized subjects. Thus, mean plasma glucagon concentration rose by about 30 pmol/l and mean plasma PP concentration by about 150 pmol/l in each group. We conclude that the release of glucagon and PP during hypoglycaemia does not depend upon changes in plasma adrenaline concentration in man.

The role of catecholamines in the control of gastrin and acid secretion during insulin hypoglycaemia in man.

5 adrenalectomized subjects and 8 healthy volunteers underwent an insulin test during which acid secretion and plasma adrenaline, noradrenaline, dopamine and gastrin concentrations were measured. Plasma glucose concentration fell by greater than 50% in all subjects. The mean plasma adrenaline concentration increased markedly (greater than 1,000%) in the normal group but was unchanged in the adrenalectomized group. In all subjects, plasma noradrenaline concentration increased moderately, whereas plasma dopamine levels remained unchanged. Clear-cut increments in plasma gastrin concentration were seen only on 3 participants, each of whom responded to insulin hypoglycaemia with an extremely high adrenaline release. Basal and peak acid output were similar in adrenalectomized and normal subjects. The results suggest that circulating catecholamines contribute to the control of gastrin and acid secretion in man only during circumstances with high plasma catecholamine levels, e.g. severe stress.

Conversion of plasma progesterone to deoxycorticosterone in men, nonpregnant and pregnant women, and adrenalectomized subjects.

During the third trimester of human pregnancy the concentrations of deoxycorticosterone (DOC) in maternal plasma are 4-50 times those in nonpregnant women and men. It has been suggested that the increased amount of DOC in maternal plasma originates in the fetal compartment. We considered an alternate explanation for the high levels of DOC in plasma or near-term pregnant women, viz., that DOC may be derived in part from 21-hydroxylation of maternal plama progesterone. To test this hyposthesis we measured the fractional conversion of plasma progesterone to DOC from the relationship between the 3H:14C ratio of the infused tracers, [3H]progesterone and [14C]-DOC, and the 3H:14C ratio or urinary 3 alpha,21-dihydroxy-5 beta-pregnan-20-one (tetrahydro-DOC). The fractional conversion of plasma progesterone to DOC ([rho](BU)P-DOC), measured in this manner, was 0.007 +/- 0.001 (mean +/- SEM, n = 26) in the subjects of this study. The values for [rho](BU)P-DOC varied widely among subjects (0.002-0.022) but the range of values for [rho](BU)P-DOC was similar among women pregnant with an anencephalic or dead fetus, nonpregnant and adrenalectomized women, and men. The transfer constant of conversion of progesterone to DOC in plasma, [rho](BB)P-DOC, remained constant in a nonpregnant woman during the infusion of nonradiolabeled progesterone at rates of 0-14 mg/h. Based on the results of these studied, we conclude that DOC is formed by extra-adrenal 21-hydroxylation of plasma progesterone and that the rate of formation of DOC by this pathway is proportional to the concentration of progesterone in plasma.

Improved biochemical characterization of breast cancer as a guide to hormonal treatment.

Theoretically, all estrogen-receptor positive (ER+) tumors of the breast should respond to hormonal therapy; however, only 50-60% do. Therefore, this study collected information on hormonal variations which affect the cytoplasmic receptor levels and offers other parameters besides estrogenicity for biochemically characterizing breast cancers. One reason ER+ does not insure hormonal responsiveness is that cytoplasmic receptor levels are influenced by endogenous hormones as well as by exogenous factors, specifically rhythmic fluctuations of unknown origin (circadian and seasonal). Because of these various influences, it is obvious that no normal baseline level of receptors in target tissue exists on which to place the decision for prognosis of hormonal therapy. In addition to quantitative assessment of ER by assay, determination of nuclear estradiol content and measurement of cytoplasmic progestin receptor must be employed. Experiments outlined have shown that the receptor can enter the nucleus of target tissue without the assistance of hormone. Hence, complete hormone withdrawal (as in ovariectomized and adrenalectomized subjects) is not a totally effective treatment for hormone-responsive cancers. Instead, this withdrawal must be supplemented by an antihormonal treatment that incapacitates the receptor. In this article, the virtue of tamoxifen for performing this blockade is pointed out. Since tamoxifen competes with estradiol at the receptor-binding site (according to pig uterus experiments outlined here), its biological effect might be explained by a blockade of the nuclear ER transfer, the parameter that hormonal withdrawal alone cannot affect.

Sympathetic control of hepatic glycogenolysis during glucopenia in man

Liver glycogen stores may be mobilized during hypoglycemia by release of adrenomedullary catecholamines, by release of norepinephrine from sympathetic nerve endings and by release of glucagon. To clarify the nature of peripheral sympathetic control of hepatic glycogenolysis during glucopenia in man, 2-deoxy-d-glucose (2 DG), a competitive inhibitor of glucose metabolism, was infused intravenously (50 mg/kg) to nine normal volunteers and four adrenalectomized patients for 20 min. In normal volunteers, the initial elevation of free fatty acids (FFA) and growth hormone (HGH) correspond with the rise in total catecholamines, with maximal levels attained at 60 min; lactate and cortisol rose at a slower rate, no change in IRI was noted. Plasma glucose levels were 148% of preinfusion values by 120 min and remained elevated. In adrenalectomized subjects, despite no change in plasma FFA, lactate, catecholamines and glucagon, glucose rose 20% by 150 min; the growth hormone and insulin responses were similar to normals. A significant increase in glucose response from 60 min onward was found in the 2 DG infusion studies when compared to cortisone administration, alone. Thus, during glucopenia, plasma glucose rose in spite of unchanged adrenomedullary catecholamine and glucagon levels. The findings indicate that the sympathetic neurotransmitter, norepinephrine, contributes to counterregulatory events during 2 DG-induced glucopenia presumably via its release from hepatic sympathetic nerve endings.

Estimation of aldosterone, 11-deoxycorticosterone, 18-hydroxy-11-deoxy-corticosterone, corticosterone, cortisol and 11-deoxycortisol in human plasma by gas-liquid chromatography with electron capture detection.

A method for determining the plasma concentrations of six major corticosteroids, aldosterone, 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), corticosterone, deoxycorticosterone (DOC), cortisol and 11-deoxycortisol using gas-liquid chromatography with electron capture detection is described. Esterification of suitable derivatives of these compounds with heptafluorobutyric anhydride (HFB) allowed detection of quantitities of steroid, ranging from 0-3 pg for androstenetrione HFB (from cortisol) to 2-3 pg for corticosterone HFB. No detectable reagent blank was obtained for any compound when water was used instead of plasma and this was also the case when plasma from an adrenalectomized subject was analysed, with the exception of 18-OH-DOC where a reproducible but negligibly small blank occurred. Coefficients of variation for replicate determinations ranged from 8% for corticosterone to 17% for aldosterone. Concentrations in a series of normal human plasma samples were as follows: aldosterone, 4-0- 18-0 ng/100 ml; 18-OH-DOC, 20-16- ng/ml; corticosterone, 0-08 - 0.-80 mug/100 ml; DOC, 2-8 - 16-0 ng/100 ml; cortisol, 2-5 - 10-0 mug/100 ml; and 11-deoxycortisol, 40-0 - 400-0 ng/100 ml. When seven normal subjects were treated with dexamethasone concentrations of DOC, cortisol and 11-deoxycortisol fell to below the limit of the normal range, those of 18-OH-DOC and corticosterone were at the lower end of the normal range while the concentration of aldosterone was not significantly affected.

The estimation of plasma 11-deoxycorticosterone in man using gas-liquid chromatography with electron capture detection.

SUMMARY A method of estimating the peripheral plasma concentration of 11-deoxycorticosterone (DOC) in man by means of gas-liquid chromatography with electron capture detection is described. Purification requirements for samples and chromatographic media have been simplified by the use of a detector bypass valve which reduces the risk of detector contamination. For this reason the method is relatively short. There was no measurable blank using either plasma from an adrenalectomized subject or water. The normal range was found to lie between 4·1 and 17·2 ng/100 ml (mean 9·8). Dexamethasone administration to one subject resulted in a subnormal plasma DOC concentration.

Adrenalectomy: Effects on mating behavior, ovulation, and early gestation in the cycling rat

Adrenalectomy was performed 4 weeks prior to evaluating the effects on mating behavior, ovulation, and the first 10 days of gestation in 4-day cycling female rats. Mating behavior was essentially normal and occurred at times similar to sham-adrenalectomized animals on the afternoon of predicted proestrus. The number of ova ovulated was significantly reduced in mated adrenalectomized subjects in contrast to data reported by Rodgers (1971) for intact females mated at similar times in proestrus. Embryonic swellings were significantly fewer at day 10 of gestation than in the sham-adrenalectomized group providing additional evidence of reduced numbers of ova ovulated. Embryonic weights at day 10 of gestation were not affected by adrenalectomy. Removal of adrenocortical hormones significantly increased uterine weight on the morning of vaginal estrus. The data fail to show a significant delay in sexual receptivity as a result of removing adrenal progesterone, but suggest that adrenalectomy interferes with the neuroendocrine reflex mediating ovulation.

Observations on the role of the fetal adrenal gland in steroidogenesis during diabetic pregnancy.

SummaryClinical and endocrinological findings are reported in a patient with diabetes mellitus who was subjected to bilateral adrenalectomy for adrenal hyperplasia and to removal of 80 per cent of the pancreas on account of an islet cell tumour. The patient subsequently became pregnant as a result of treatment with Pergonal (Serono) and human chorionic gonadotrophin (HCG).During the gestation period levels of HCG did not differ from normal while values for oestrogens and pregnanediol were at the lower end of or below the normal range.Levels of urinary testosterone and epitestosterone during the pregnancy were considerably higher than in an adrenalectomized subject previously studied, suggesting that, in the presence of maternal diabetes, the main site of elaboration of precursors of these hormones was the fetal adrenal gland.

Cortisol metabolism in the morning and evening; relation to cortisol secretion rate measurements

The question was studied whether the discrepancies observed in cortisol secretion rate determinations from several metabolites were due to changes in metabolic pathway of cortisol during the course of the day. Cortisol-4- 14C was administered to two subjects in the morning at about 0800 hr. The studies were repeated in the same subjects twice in the evening at about 1800 hr and one subject received cortisol-4- 14C at 1415 hr as well. The specific activities of 6 metabolites were determined and the apparent cortisol secretion rates were calculated. The production rates from the various metabolites were not in precise agreement at any of the times of day studied; the disagreement was apparently greatest when the tracer was given in the evening. That the time of day at which labeled cortisol is injected is not the factor responsible for the different estimates was shown in an adrenalectomized subject maintained on dexamethasone. Tracer cortisol-4- 14C was given to this patient at 1750 hr and 36 hours later another tracer of cortisol 1,2- 3H was given at 0900 hr. Complete urine collections were obtained from the time of administration of the first tracer until 36 hours after the second. The urine was processed as a single collection. The 3H/ 14C ratios of all the metabolites were identical demonstrating that the labeled cortisol followed identical metabolic pathway in the morning and in the evening. It thus appears that a diurnal variation in cortisol metabolizing enzymes is not responsible for the demonstrated discrepancies between metabolites when secretion rate is measured by the isotope dilution method from urinary metabolites.

Plasma glucose response to natural vasopressin in maturity onset diabetics and adult nondiabetics

Plasma glucose rose following natural vasopressin injection in 9 maturity onset diabetic and 14 adult nondiabetic subjects. The rise was sustained throughout the 2-hour test period. No significant changes in plasma insulin and growth hormone occurred. Stimulation of adrenocortical and adrenomedullary secretions were not essential factors, as the response occurred in bilaterally adrenalectomized subjects. It is suggested that natural vasopressin may have a direct glucose elevating action perhaps mediated via Cyclic AMP activation of hepatic phosphorylase.