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Biomedical subjects

P Brunetti

Publications and source records attributed to P Brunetti.

At least 127 records · Page 7Linked to original sources
PubMed1987

Effect of exogenously administered estrogens on luteinizing hormone release in a complete testicular feminization syndrome patient with very low testosterone levels, before and after gonadectomy.

The response of LH to exogenously administered estrogens was evaluated in a 63-year-old patient affected by complete testicular feminization syndrome (CTFS) with very low testosterone (T) levels, before and after gonadectomy. Prior to gonadectomy a durative fall in gonadotropin levels was observed after estrogen administration, without observing of an estrogenic positive feed-back (EPF) from LH. After gonadectomy, following an initial decrement in both gonadotropins, the characteristic. LH peak was seen, 48 h after E2B (Estradiol Benzoate) administration. This observation, together with the very low T levels that we found in this patient, prompted us to construe that absence of EPF in males is not due, as previously believed, to a direct inhibitory action of T or E2, deriving from T aromatization, on the hypothalamus, but by a still unknown gonadal factor. The hypothesis that this factor has a tubular origin is formulated and discussed.

Androgen-Insensitivity Syndrome↗
PubMed1987

The pancreatic-adrenocortical-pituitary clamp technique for study of counterregulation in humans.

The present experiments were undertaken to develop an approach to analyze the contribution of individual glucose counterregulatory hormones in humans. For this purpose, 24 normal subjects were studied twice: once (control experiments) hypoglycemia was induced by subcutaneous infusion of insulin; and once [pancreatic-adrenocortical-pituitary (PAP) clamp technique] the spontaneous responses of plasma glucagon, growth hormone, and cortisol to hypoglycemia were prevented by intravenous somatostatin and oral metyrapone, respectively, and each hormone was infused at variable rates, which reproduced spontaneous changes in their circulating concentrations in the control experiments. Plasma glucose rate of decrease (0.052 +/- 0.003 vs. 0.06 +/- 0.003 mg X dl-1 X min-1), plasma glucose nadir (49.8 +/- 1.2 vs. 50 +/- 1.0 mg/dl), initial suppression of glucose production (0.22 +/- 0.01 vs. 0.23 +/- 0.01 mg X kg-1 X min-1), subsequent compensatory increase in glucose production (0.54 +/- 0.05 vs. 0.48 +/- 0.04 mg X kg-1 X min-1), and the increase in glucose utilization (0.45 +/- 0.05 vs. 0.42 +/- 0.05 mg X kg-1 X min-1) in PAP clamp and control experiments, respectively, were not significantly different and were significantly correlated. Changes in plasma alanine, lactate, free fatty acids, 3-beta-hydroxybutyrate concentrations were also virtually identical in the PAP clamp experiments and in control experiments. We conclude that the PAP clamp technique can faithfully reproduce the spontaneous hormonal and substrate responses to hypoglycemia and should be useful to assess the contribution of individual hormones during counterregulation by creating an isolated (total or partial) deficiency of a particular hormone without confounding compensatory changes in secretion of other counterregulatory hormones.

3-Hydroxybutyric Acid↗
PubMed1986

Studies on overnight insulin requirements and metabolic clearance rate of insulin in normal and diabetic man: relevance to the pathogenesis of the dawn phenomenon.

In order to assess whether the metabolic clearance of insulin changes overnight, 11 patients with Type 1 (insulin-dependent) diabetes and low insulin antibody titre, and 6 nondiabetic subjects were studied. In these studies insulin was always infused by a Harvard pump. Initially, the nocturnal insulin requirements were assessed in the diabetic patients by an overnight feedback insulin infusion to maintain euglycaemia. The insulin requirements decreased continuously after midnight to a nadir of 0.115 +/- 0.014 mU X kg-1 X min-1 at 04.30 hours, but after 05.00 hours the insulin requirements increased nearly 40 percent to a maximum of 0.16 +/- 0.012 mU X kg-1 X min-1 at 07.00 hours. To assess whether plasma insulin clearance changes overnight, the diabetic patients were studied on two different occasions, from 22.00-02.30 hours and from 04.00-08.30 hours. During each of these two studies insulin was infused in sequential steps of 90 min each at the rate of 0.13, 0.40 and 0.20 mU X kg-1 X min-1. Despite changes in plasma free insulin concentration, the metabolic clearance of insulin in the interval 22.00-02.30 hours (12.6 +/- 0.17 ml X kg-1 X min-1) was no different from that of the interval 04.00-08.30 hours (12.5 +/- 0.19 ml X kg-1 X min-1). The nondiabetic subjects were studied on two different occasions to assess whether the metabolic clearance of insulin changes overnight. Somatostatin (0.25 mg/h) and insulin (0.3 mU X kg-1 X min-1) were infused from 22.00-02.30 hours on one occasion, and from 04.00-08.30 hours on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Comparison of glucose counterregulation during short-term and prolonged hypoglycemia in normal humans.

To compare glucose counterregulatory mechanisms during short-term hypoglycemia and prolonged hypoglycemia, insulin was infused either intravenously (160 mU X M-2 X min) for 10 min or subcutaneously (15 mU X M-2 X min) for 12 h in normal volunteers. With each type of insulin infusion, hypoglycemia (approximately 50 mg/dl) was either allowed to develop or was prevented (control experiments) by the glucose-clamp technique. During prolonged hypoglycemia, both increased glucose production (1.55 +/- 0.05 versus 0.33 +/- 0.14 mg X kg-1 X min in control experiments at 12 h, P less than 0.01) and suppressed glucose utilization (1.55 +/- 0.06 versus 3.17 +/- 0.15 mg X kg-1 X min in control studies at 12 h, P less than 0.01) were involved in counterregulation. During short-term hypoglycemia, only increased glucose production (3.23 +/- 0.33 versus 0.06 +/- 0.03 mg X kg-1 X min in control experiments at 60 min) was involved, since glucose clearance actually increased (3.99 +/- 0.20 versus 2.88 +/- 0.02 ml X kg-1 X min in control experiments at 60 min, P less than 0.01). Estimated portal venous insulin concentrations decreased 40% (basal 24 +/- 3 versus 14 +/- 1 mU/ml at 60 min, P less than 0.01) in the short-term hypoglycemia experiments but remained at basal levels (basal 25 +/- 1 versus approximately 26 microU/min between 1 and 12 h) during prolonged hypoglycemia. Despite the fact that hypoglycemia was more gradually induced in the prolonged hypoglycemia model, peak counterregulatory hormone responses were at least as great as those during short-term hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Role of hepatic autoregulation in defense against hypoglycemia in humans.

To assess the role of hepatic autoregulation in defense against hypoglycemia, we compared the effects of complete blockade of glucose counterregulation with those of blockade of only neurohumoral counterregulation during moderate (approximately 50 mg/dl) and severe (approximately 30 mg/dl) hypoglycemia induced by physiologic hyperinsulinemia during subcutaneous infusion of insulin in normal volunteers. Compared with observations in control experiments, neurohumoral counterregulatory blockade (somatostatin, propranolol, phentolamine, and metyrapone), during which identical moderate hypoglycemia was achieved using the glucose clamp technique, resulted in suppressed glucose production (0.62 +/- 0.08 vs. 1.56 +/- 0.07 mg/kg per min at 12 h, P less than 0.01) and augmented glucose utilization (2.17 +/- 0.18 vs. 1.57 +/- 0.07 mg/kg per min at 12 h, P less than 0.01). Complete blockade of counterregulation (neurohumoral blockade plus prevention of hypoglycemia) did not further enhance the suppressive effects of insulin on glucose production. However, when severe hypoglycemia was induced during neurohumoral counterregulatory blockade, glucose production was nearly two times greater (1.05 +/- 0.05 mg/kg per min at 9 h) than that observed during complete counterregulatory blockade (0.58 +/- 0.08 mg/kg per min at 9 h, P less than 0.01) and that observed during mere neurohumoral blockade with moderate hypoglycemia (0.59 +/- 0.06 mg/kg per min at 9 h, P less than 0.01). These results demonstrate that glucose counterregulation involves both neurohumoral and hepatic autoregulatory components: neurohumoral factors, which require only moderate hypoglycemia for their activation, augment glucose production and reduce glucose utilization; hepatic autoregulation requires severe hypoglycemia for its activation and may thus serve as an emergency system to protect the brain when other counterregulatory factors fail to prevent threatening hypoglycemia.

Adrenergic alpha-Antagonists↗
PubMed1984

Metabolic effects of intensified insulin therapy.

Intensified insulin therapy is usually carried out either with multiple subcutaneous insulin injections (ICT: intensified conventional therapy) or with continuous subcutaneous insulin infusion (CSII) by minipumps. For two years we have been studying two matched groups of type I diabetic patients, treated with 3 daily insulin injections (ICT) and with CSII ( Microjet , Miles), respectively. Blood glucose control, as assessed by integrated mean blood glucose (MBG), was similar in both groups, but a better metabolic stability ('M' index of Schlichtkrull ) was evident in the CSII group. From the 24-hour profiles of plasma 'free' IRI and metabolites (glucose, beta-OH-butyrate, lactate, pyruvate, alanine), both the hepatic and peripheral underinsulinization and related metabolic alterations were still evident in both groups of patients. The number of hypoglycaemic episodes, recorded by home blood glucose monitoring, was similar in both groups of patients, while the perception of symptomatic hypoglycaemia seemed to be reduced in the patients treated with CSII.

Alanine↗
PubMed1984

Does the hypothalamic tyrosine-hydroxylase inhibition mediate the positive feedback of progesterone on gonadotropin release in women?

Neuropharmacological studies suggest a common inhibitory role for the hypothalamic dopaminergic pathway on gonadotropin and prolactin pituitary release, in humans. As a consequence, it has been hypothesized that the inhibition of hypothalamic tyrosine-hydroxylase and the subsequent fall in dopamine synthesis is involved in the positive feedback of progesterone on LH and PRL pituitary release in estrogen-primed hypogonadal women. The aim of our study was to verify whether an inhibition of tyrosine-hydroxylase may really account for the progesterone action on gonadotropin and prolactin secretion. For this purpose, we compared the effect of a specific tyrosine-hydroxylase inhibitor (alpha-methyl-p-tyrosine, AMPT) with the effect of progesterone on gonadotropin and prolactin release in estrogen-primed postmenopausal women. Progesterone induced a marked release of LH (delta: 129.7 +/- 16.5 mlU/ml, mean +/- SE) and a slight increase in FSH (delta: 39.4 +/- 11.6 mlU/ml) and PRL (delta: 15.3 +/- 2.8 ng/ml) serum levels. Acute or two-day administration of AMPT was followed by a marked rise in PRL serum levels (delta: 82.9 +/- 13.8 and 88.3 +/- 8.2 ng/ml, respectively) while there were no significant increases in serum LH (delta: 5.4 +/- 2.6 and 3.3 +/- 4.6 mlU/ml) and FSH (delta: 3.4 +/- 0.9 and -0.4 +/- 2.9) concentrations. The ineffectiveness of a specific tyrosine-hydroxylase inhibitor in simulating the progesterone effect on gonadotropin secretion seems to negate the hypothesis that a reduction in hypothalamic dopaminergic activity mediates the positive feedback of progesterone on gonadotropin release.

Aged↗
PubMed1984

Catecholamines and pituitary function. 2. Prolactin response to different dopamine doses in normal cycling women and patients with prolactin-secreting pituitary tumors, both before and after endogenous catecholamine synthesis inhibition.

The inhibitory effect of various doses of dopamine on serum PRL levels was assessed in both normal cycling women and patients with tumoral hyperprolactinemia before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine, a strong and specific tyrosine-hydroxylase inhibitor. Dopamine infusion induced a significant decrease in the serum PRL levels in both normal cycling and hyperprolactinemic subjects. The mean percent inhibition of baseline PRL induced by the various dopamine infusion rates (0.1, 0.5, 1.0 and 2.0 micrograms/kg/min) was similar in regularly cycling women and in patients with tumoral hyperprolactinemia both before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine. Alpha-methyl-p-tyrosine pretreatment significantly increased serum PRL concentrations in normal women and enhanced their responsiveness to the exogenously administered dopamine. Hyperprolactinemic patients, on the contrary, did not show any significant variation in either basal PRL release or the PRL sensitivity to dopamine infusion after endogenous catecholamine synthesis inhibition. These data indicate that reduced dopamine delivery to the adenomatous lactotroph, either due to a primary hypothalamic abnormality or to a deranged vascular pituitary arrangement, rather than a reduced PRL sensitivity to dopamine inhibition, is the main event accounting for PRL hypersecretion in women with PRL-secreting pituitary tumors.

Catecholamines↗
PubMed1984

Catecholamines and pituitary function. I. Effects of catecholamine synthesis inhibition and subsequent catecholamine infusion on gonadotropin and prolactin serum levels in normal cycling women and in women with hyperprolactinemic amenorrhea.

To investigate the role of catecholamines in the control of gonadotropin and prolactin release, we examined the effects of a catecholamine synthesis inhibitor (alpha-methyl-p-tyrosine, AMPT) administration and those of dopamine (DA) or epinephrine (EPI) infusion after endogenous catecholamine synthesis inhibition, on FSH, LH and PRL serum levels, in regularly cycling women and in patients with hyperprolactinemic amenorrhea. AMPT administration was followed by a prompt increase in serum PRL in regularly cycling women, but not in women with hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or 'idiopathic'. Gonadotropin serum levels did not show any significant variation after AMPT in both normal and hyperprolactinemic women. DA infusion after endogenous catecholamine synthesis inhibition by AMPT, induced an appreciable decline in PRL levels in both normal and hyperprolactinemic subjects. Although the net decrements were higher in the hyperprolactinemic group, the PRL fall was similar in the two groups when expressed as a percentage of preinfusion PRL concentrations. LH serum levels similarly fell during DA infusion in normal women and in hyperprolactinemic patients, while FSH concentrations did not show any significant change. EPI infusion after analogous AMPT pretreatment was followed by an evident decrease in serum PRL in both normal and hyperprolactinemic subjects. No significant changes in FSH and LH serum concentrations were observed during EPI administration. These data, while confirming the existence of a functional derangement in the neural inhibitory control of PRL secretion in hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or so-called 'idiopathic', do not agree with the hypothesis that tubero-infundibular DA hyperactivity inhibits gonadotropin secretion in hyperprolactinemic patients. The inhibitory action of exogenously administered DA might represent rather a pharmacological effect than express a physiological inhibitory role of hypothalamic DA pathway on gonadotropin secretion in humans.

Adult↗
PubMed1984

Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia.

To elucidate the mechanisms controlling the response of glucagon to hypoglycemia, a vital component of the counterregulatory hormonal response, the role of intraislet insulin was studied in seven normal subjects and five subjects with insulin-dependent diabetes mellitus (IDDM) (of less than 15-mo duration). In the normal subjects, hypoglycemia (arterial plasma glucose [PG] 53 +/- 3 mg/dl) induced by an intravenous insulin infusion (30 mU/m2 X min for 1 h, free immunoreactive insulin [FIRI] 58 +/- 2 microU/ml) elicited a 100% fall in insulin secretion and an integrated rise in glucagon of 7.5 ng/ml per 120 min. When endogenous insulin secretion was suppressed by congruent to 50 or congruent to 85% by a hyperinsulinemic-euglycemic clamp (FIRI 63 +/- 1.5 or 147 +/- 0.3 microU/ml, respectively) before hypoglycemia, the alpha cell responses to hypoglycemia were identical to those of the control study. When the endogenous insulin secretion was stimulated by congruent to 100% (hyperinsulinemic-hyperglycemic clamp, FIRI 145 +/- 1.5 microU/ml, PG 132 +/- 2 mg/dl) before hypoglycemia, the alpha cell responses to the hypoglycemia were also superimposable on those of the control study. Finally, in C-peptide negative diabetic subjects made euglycemic by a continuous overnight intravenous insulin infusion, the alpha cell responses to hypoglycemia were comparable to those of normal subjects despite absent beta cell secretion, and were not affected by antecedent hyperinsulinemia (hyperinsulinemic-euglycemic clamp for 2 h, FIRI 61 +/- 2 microU/ml). These results indicate that the glucagon response to insulin-induced hypoglycemia is independent of the level of both endogenous intraislet and exogenous arterial insulin concentration in normal man, and that this response may be normal in the absence of endogenous insulin secretion, in contrast to earlier reports. Thus, loss of beta cell function is not responsible for alpha cell failure during insulin-induced hypoglycemia in IDDM.

Adult↗
PubMed1984

Demonstration of a dawn phenomenon in normal human volunteers.

To ascertain whether the dawn phenomenon occurs in nondiabetic individuals and, if so, whether it is due to an increase in glucose production or a decrease in glucose utilization, we determined plasma concentrations of glucose, insulin, C-peptide, and counterregulatory hormones, as well as rates of glucose production, glucose utilization, and insulin secretion at one-half-hourly intervals between 1:00 and 9:00 a.m. in eight normal volunteers. After 5:30 a.m., plasma glucose, insulin, and C-peptide concentrations all increased significantly; rates of glucose production, glucose utilization, and insulin secretion also increased (all P less than 0.05). Plasma cortisol, epinephrine, and norepinephrine increased significantly from nocturnal nadirs between 4:00 and 6:30 a.m. Plasma growth hormone, which had increased episodically between 1:00 and 4:30 a.m., decreased thereafter nearly 50% (P less than 0.05). Plasma glucagon did not change significantly throughout the period of observation. These results indicate that a dawn-like phenomenon, initiated by an increase in glucose production, occurs in nondiabetic individuals. Thus, early morning increases in plasma glucose concentrations and insulin requirements observed in IDDM and NIDDM may be an exaggeration of a physiologic circadian variation in hepatic insulin sensitivity induced by antecedent changes in catecholamine and/or growth hormone secretion.

Adult↗
PubMed1984

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus.

To assess the effects of glycemic control on glucose counterregulation, rates of plasma glucose recovery from hypoglycemia and counterregulatory hormonal responses were studied in 18 C-peptide-negative patients with insulin-dependent diabetes mellitus (IDDM) before and after either improvement, no change, or deterioration in glycemic control. Hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 X min for 1 h) after maintenance of euglycemia overnight with i.v. insulin. In 13 patients with long duration of IDDM (9 +/- 0.5 yr, mean +/- SEM) and initially poor glycemic control (mean diurnal blood glucose, MBG 199 +/- 8 mg/dl, ketoamine-HbA1 12.4 +/- 0.2%; nondiabetic subjects 104 +/- 4 mg/dl and 6.8 +/- 0.09%, respectively), rates of plasma glucose recovery from hypoglycemia (0.30 +/- 0.01 versus 0.60 +/- 0.01 mg/dl X min in nondiabetic subjects, P less than 0.001) and plasma glucagon (AUC 0.56 +/- 0.09 versus 6.3 +/- 0.50 ng/ml X 150 min in nondiabetic subjects, P less than 0.01) and epinephrine (AUC 16.9 +/- 0.2 versus 25.7 +/- 0.2 ng/ml X 150 min in nondiabetic subjects, P less than 0.001) responses to hypoglycemia were impaired. Intensive therapy (three daily injections of insulin) instituted in 7 out of 13 IDDM patients for up to 9 mo improved MBG (124 +/- 6 mg/dl, P less than 0.01) and ketoamine-HbA1 (7.9 +/- 0.02%, P less than 0.01) but not rates of plasma glucose recovery (0.31 +/- 0.01 mg/dl X min) and plasma glucagon (AUC 0.69 +/- 0.07 ng/ml X 150 min) and epinephrine (AUC 14.9 +/- 0.17 ng/ml X 150 min) responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus.

The safety, reproducibility, and reliability of an insulin infusion test for assessment of adequate glucose counterregulation were evaluated in 18 patients with type I (insulin-dependent) diabetes mellitus. When the test (a 60-min, 30-mU/m2/min insulin infusion) was administered on three separate occasions at 3-4-wk intervals, coefficients of variation for plasma glucose and counterregulatory hormone (glucagon, epinephrine, cortisol, and growth hormone) responses averaged less than 8%. No patient experienced symptoms requiring discontinuation of the test and plasma glucose concentrations increased spontaneously after stopping the insulin infusion. Using objective criteria based on plasma glucose nadirs or postnadir rates of plasma glucose recovery, no patient judged to have adequate glucose counterregulation by the test (postnadir rates of plasma glucose recovery or plasma glucose nadir above 0.4 mg/dl/min and 45 mg/dl) developed severe hypoglycemia (plasma glucose less than 40 mg/dl) during up to 7 mo of intensive insulin therapy, whereas nearly all patients with inadequate counterregulation did. We conclude that this test, when performed in standardized conditions, is safe and reproducible and can reliably predict those patients with type I diabetes who are at risk of developing severe hypoglycemia during intensive insulin therapy.

Adolescent↗