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Biomedical subjects

C De Palo

Publications and source records attributed to C De Palo.

At least 19 recordsLinked to original sources

Effect of naltrexone treatment on insulin secretion, insulin action and postprandial thermogenesis in obesity.

For many years a series of studies has been carried out to evaluate the role of endogenous opioid peptides on glucose metabolism. In this work we studied the influence of endogenous opioid peptides on insulin response to OGTT and glucose-induced thermogenesis before and after a prolonged oral treatment with Naltrexone (50 mg/daily for 6 days), an opioid receptor antagonist, in a group of 9 obese subjects. Moreover in obese patients we evaluated the effect of this anti-opioid drug on insulin secretion and insulin sensitivity during an IVGTT using the minimal model approach. We compared the pre-treatment results with data coming from a group of 5 normal-weight subjects. We measured blood glucose, plasma insulin and C-peptide concentrations and evaluated the following parameters: first (phi 1) and second (phi 2) phase of beta-cell sensitivity, insulin sensitivity and glucose effectiveness. Obese subjects displayed an increased insulin response to oral and i.v. glucose load, due to an increased first phase of insulin secretion (phi 1), a reduced insulin sensitivity (Si) and glucose effectiveness (Sg) in respect to normal-weight subjects. They showed no difference in glucose and insulin area during oral load and in their profiles during i.v. glucose load after naltrexone treatment. Similarly no significant variation in insulin sensitivity and glucose effectiveness was observed. The glucose-induced thermogenesis, measured by indirect calorimetry, was not modified by naltrexone. Therefore our study demonstrates that endogenous opioids do not play any role in the impairment of peripheral insulin sensitivity and energy expenditure in human obesity.

Adult↗

Plasma acetyl-carnitine concentrations during and after a muscular exercise test in patients with liver disease.

In many human tissues, fuel is stored for immediate use, as well as for energy exchange between different parts of the body. Fat and glycogen represent, together with proteins, the principal energy storage materials. During energy requirement, e.g. muscular exercise, glycogen as a local reserve, is used first to supply energy needs. Acetyl-carnitine, as an active molecular group, represents an intermediate substrate, usable directly in the working tissue. The present study investigates whether plasma acetyl-carnitine could be a useful biochemical measure for information on fuel exchange in the body, and whether it is a rapidly available energy source exchangeable among tissues with different metabolic functions, such as muscle and liver. The present study investigated control and hepatopathic subjects after maximal and submaximal muscular exercise. Hepatopathic patients may be a useful model, as liver carnitine metabolism is likely to be impaired. Plasma acetyl-carnitine before, during and after maximal exercise in hepatopathic subjects did not differ, while in normal subjects it increased. After submaximal exercise, acetyl-carnitine increased in patients, as well in controls. In the patients (n = 9) with liver metabolism disorders we observed that during maximal exercise plasma acetyl-carnitine varied from 3.26 +/- 2.18 mumol/l (time 0 min) to 4.30 +/- 2.02 mumol/l (time 20 min) and from 1.99 +/- 1.36 mumol/l to 4.83 +/- 2.60 mumol/l (p less than 0.05) in the controls (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcarnitine↗

Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis.

In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.

Amyotrophic Lateral Sclerosis↗

Resistance to a long-acting somatostatin analog (SMS 201-995) reversed by surgery in acromegaly.

A 42-year-old woman had acromegaly and a large macroadenoma with supra- and parasellar extension. Her GH levels (median 85 ng/ml, range 63-170 ng/ml) were not responsive to TRH (200 micrograms iv), GHRH (100 micrograms iv) and bromocriptine (Br 2.5 mg po) acute tests; Sm-C level was 8 U/ml. She was treated with octreotide (SMS) (up to 1500 micrograms daily) for 3 months. No changes of clinical, biochemical and radiological findings were seen, therefore she underwent transsphenoidal surgery. After surgery, hypopituitarism and diabetes insipidus appeared: GH levels remained high (median 45 ng/ml; range 37-56 ng/ml), but became responsive to Br acute test. The patient was given SMS again, and this resulted in clinical improvement, marked reduction of GH and Sm-C levels and slight shrinkage of the residual tumor. Speculative hypotheses about this previously unreported phenomenon might be either an excess of both GHRH and somatostatin, caused by a primary increase of dopaminergic tone, or a primary excess only of GHRH; in both cases the surgical lesion of the hypothalamic-pituitary region might have impaired the neurohormones inflow to the residual pituitary and so let SMS and Br exert their inhibitory actions on GH secretion.

Acromegaly↗

Human growth hormone association and binding study in vitro: high performance size exclusion chromatography and radioimmunoassay-measured levels in plasma of normal and acromegalic subjects.

Human growth hormone (hGH), like other protein hormones, consists of several molecular forms both in the pituitary and in plasma. In recent years carrier proteins have been detected and studied for growth hormone, using different experimental approaches. In the present study we have attempted to investigate whether hGH could be separated and identified in molecular or aggregated forms using high performance size exclusion chromatography and a small plasma sample, without particular treatment, in order to investigate specific hGH-binding proteins in normal as well as in acromegalic subjects. Results showed that it was possible to observe binding or/and the formation of a complex between free hormone and other molecules that could be specific binding proteins. Equilibrium was reached in a few minutes (7-10 min) and was reversible, as observed with labelled hormone using low and high concentrations of hGH in the incubation medium. At 37 degrees C the associated form at equilibrium was 30% of the total (measured as percent of total radioactivity with labelled hormone) in a plasma medium in which the original growth hormone was absent. Acromegalic plasma demonstrated that the percent of the associated form (namely the 80-kDa form) was less than that in normal humans. This may be due to the fact that capacity binding and competition between labelled and non-labelled growth hormone were favorable to the non-labelled form, if only for the high concentrations in this type of pathology. Therefore our results seem to be in agreement with the hypothesis that acromegalic subjects do not lack this aggregation capacity.

Acromegaly↗

Effect of prolonged physical exercise on muscular phospholipase A2 activity in rats.

Prolonged muscular exercise stimulates glucose uptake by the working muscles themselves. The mechanism of this phenomenon is at present unclear. It has been proposed that the kallikrein-kinin-prostaglandin system plays a role in the physiological regulation of muscular glucose metabolism during exercise. Since bradykinin can stimulate phospholipase A2, a key enzymatic step in prostaglandin synthesis, phospholipase A2 activity was assayed in rats at rest and in rats compelled to swim for 60 minutes. The physiological significance of an increase in muscular phospholipase A2 activity is not clear. Since bradykinin can stimulate both muscular glucose uptake and phospholipase A2 activity, it is possible that the increased activity of this enzyme is involved in the exercise-induced increase of muscular glucose uptake. Phospholipase A2 activity was strongly increased in the exercising rat muscles. A small but significant increase in phospholipase A2 activity was observed in the heart, whereas no variation in activity was demonstrated in either the kidney or the liver of exercising rats. These findings strongly indicate that prolonged exercise increases muscular phospholipase A2 activity only in the muscle and heart. This phenomenon appears to be strongly related to muscular contraction, since other stress situations such as cold exposure did not modify phospholipase A2 activity. Our data are in agreement with the hypothesis of a possible involvement of prostaglandins in the priming action of insulin on glucose uptake during muscular work.

Animals↗

Plasma carnitine and acetyl-carnitine levels at different times of the day.

An interest in both biochemical and clinical carnitine investigation has recently developed. A more complete and extensive study is obtained if acetyl-carnitine as well as carnitine are investigated. This research, using an improved and simplified method for carnitine and acetyl-carnitine determination in the same sample (1 ml) without radioisotopic tracer use, investigates if there are the same differences in their plasma levels at different times of the day. The sample was eluted in a chromatographic column (55 X 15 mm) containing Sephadex G-25M with phosphate buffer (25 mmol/l, pH 7.4). The fraction containing acetyl and free carnitine was divided and employed separately for two assays. The carnitine assay uses an enzymatic reaction catalyzed by carnitine acetyl-transferase (CAT) and measurements are carried out spectrophotometrically. The calibration curve shows r = 0.987 and sensitivity at 5 mumol/l (reference plasma values: 38 +/- 3 mumol/l in 9 subjects). The acetyl-carnitine assay is carried out concentrating the sample by lyophilization and then measuring the enzymatic coupled reactions catalyzed by CAT, malate dehydrogenase and citrate synthase fluorimetrically. The calibration curve gives r = 0.991 and sensitivity at 1.4 mumol/l (reference plasma values: 2.8 +/- 0.3 mumol/l in 9 subjects). Both assay methods are measured at the end point. The carnitine and acetyl-carnitine measured in the plasma of 6 normal subjects at different times of the day vary respectively from 28 to 37 mumol/l and from 1.1 to 5.2 mumol/l in agreement with plasma free fatty acid (FFA) variation from 230 to 779 microEq/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcarnitine↗

Effect of exercise on plasma kallikrein and muscular phospholipase A2 activity in rats.

Many experimental observations show that prolonged physical exercise produces an increase of muscular glucose uptake. Recent findings suggest that the kallikrein-kinin-prostaglandin system may be related to this phenomenon, but so far, no direct evidence of quantitative alteration in this system has been observed during exercise. We measured plasma kallikrein and muscular phospholipase A2 activity, respectively the first and the last steps of reactions leading to prostaglandin synthesis. We demonstrated, for the first time, that during exercise plasma kallikrein activity increases in rats. We also observed an increase of muscular phospholipase A2 activity after exercise and a positive correlation between these parameters. Our findings demonstrate, under physiological conditions of enhanced muscular glucose uptake, a concomitant significant increase of plasma kallikrein and muscular phospholipase A2 activity, supporting the hypothesis that activation of the kallikrein-kinin-prostaglandin system may play some part in the enhanced muscular glucose uptake during physical activity.

Animals↗

Lack of effect of calcium infusion on blood glucose and plasma insulin levels in patients with insulinoma.

In vitro calcium plays a fundamental role in regulating insulin secretion. On the other hand, the influence of calcium excess on insulin release in vivo is not clearly defined. Recently, calcium infusion has been proposed as a provocative test for the diagnosis of insulin-secreting tumors. A 2-h infusion of calcium gluconate was performed (4 mg/kg . h) in six patients with islet cell adenoma. As a result, mean calcium plasma levels increased from 9.6 +/- 0.4 to 11.6 +/- 0.8 mg/100 ml. During calcium infusion, blood glucose and plasma insulin concentrations remained unchanged. These observations suggest that calcium fails to stimulate basal insulin secretion even in cases of organic hyperinsulinism. They show that calcium infusion is not helpful as a provocative test in the diagnosis of insulinoma.

Adenoma, Islet Cell↗

Effect of portacaval shunt on circulating free fatty acids and ketone bodies in rats.

To ascertain whether portal diversion affects ketone body (KB) metabolism, fasting circulating levels of free fatty acids (FFA), acetoacetate (AcAc) and B-hydroxybutyrate (3-OH-B) were measured in portacaval shunted (PCS), sham-operated (S-O) and unoperated control (C) rats. In PCS animals blood KB concentration was clearly reduced when compared with S-O and C rats. Beta-hydroxybutyrate level was significantly lower in PCS rats, whereas AcAc concentration did not appear significantly modified in these animals. The hypothesis is proposed that hypoketonemia induced by portal diversion is due to reduced hepatic availability of fatty acids.

Acetoacetates↗

The effect of propranolol on hypoglycaemia. Observations in five insulinoma patients.

Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not understood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.

Adenoma, Islet Cell↗

Hypoglycaemia induced by adrenal gland neoplasia (Anderson's syndrome) : report of a case.

A patient with hypoglycaemia associated with an adrenal neoplasia (Anderson's syndrome) is reported. Endocrinological investigation showed increased secretion of cortisol and catecholamines as well as an increased urinary steroid excretion along with profound inhibition of both basal and stimulated insulin secretion. During IVGTT, Conard's coefficient was reduced. The hyperglycemic response to glucagon injection was blunted, suggesting that liver glycogen stores were decreased or unavailable.

Adrenal Gland Neoplasms↗

Role of growth hormone in lipid mobilization stimulated by prolonged muscular exercise in the rat.

The effects of prolonged muscular exercise (swim in tepid water for 60 min) on blood glucose, plasma FFA and R-GH were studied in a group of normal rats and the effect on blood glucose and plasma FFA in a group of hypophysectomized rats. The data obtained showed that, whereas in normal rats plasma FFA rose after muscular exercise, plasma R-GH fell sharply. In Hypophysectomized rats, however, muscular exercise did not increase plasma FFA levels.

Animals↗