The effect of ceruletide on arterial blood pressure and heart rate: a double blind controlled study in normal volunteers.
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Biomedical subjects
Publications and source records attributed to M Alberetto.
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To investigate the possible role of gastrointestinal peptides on PRL, GH, LH, and parathyroid hormone release, bombesin (10 ng/kg . min for 60 min) and ceruletide (2 ng/kg . min for 60 min) infusions were performed in eight normal subjects. Bombesin elicited PRL release in six of eight subjects. The other hormones were not affected by either peptide. The possible effect of bombesin and ceruletide on PRL, GH, LH, and parathyroid hormone release in response to specific stimuli deserve further investigation.
Prolactin (Prl) release, both in the experimental animal and in man, is stimulated by serotonin (5HT) and inhibited by dopamine (DA). Data also suggest that LH release in the animal is stimulated by norepinephrine and inhibited by DA. The role of 5HT in the control of LH release is less clear. It would appear to stimulate episodic LH release and to inhibit the LH surge at the pro-oestrus in animals, but the effect of 5HT on LH release has not yet been evaluated in man. In the present paper we have studied the effect of various DA-ergic drugs (DA, iv l-dopa, po l-dopa and bromoergocriptine) and of two anti-5HT drugs, metergoline and methysergide, on Prl and LH release in normal women. DA-ergic drugs lowered plasma Prl and LH levels; anti-5HT drugs, at doses able to lower Prl levels, did not affect basal LH release nor the inhibiting effect of iv l-dopa on LH release. These data indicate that DA inhibits both LH and Prl release in normal women, and that 5HT stimulates Prl release but is not involved in the regulation of LH secretion. The fact that, at variance to all the DA-ergic drugs used, the two anti-5HT drugs did not vary LH release, suggests that metergoline and methysergide are devoid of DA-ergic activity in man, at least at the doses able to inhibit Prl release.
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Four euglycemic glucose-clamp studies by artificial pancreas (Biostator, Miles) have been performed during prolonged fast before and after pharmacological treatment in a patient with insulinoma. In the basal state a high glucose infusion rate (8.9 g/h) was unable to achieve the preselected blood glucose plateau of 80 mg/100 ml. The plasma insulin levels during this first glucose-clamp were comprised between 18 and 50 microunits/ml. On the first day of diazoxide treatment (300 mg/die),. the glucose infusion rate decreased to 6.4 g/h, without variation in plasma insulin level, thus suggesting a diazoxide effect independent of the inhibition of insulin secretion. After 7 days of diazoxide treatment, a further reduction of glucose infusion (5.8 g/h), together with a lowering of plasma insulin levels (7-18 microunits/ml) was observed. Both in the basal state and during diazoxide treatment a circadian pattern of glucose requirement was noted, with lower glucose need and plasma insulin levels during the night. Surgery was undertaken with glucose-clamp by artificial pancreas; blood glucose level being higher than the preselected value of 80 mg/100 ml, simple monitoring of glycemia was performed. The excision of a single adenoma was followed by a substantial rise in blood glucose 20 min later. An additional glucose-clamp, performed 3 months after surgery showed a dramatic fall of the glucose infusion rate (2.9 g/h) needed to achieve the preselected blood glucose plateau, confirming the completeness of the intervention. This experience shows that glucose-clamp by artificial pancreas may be of great value in the study as well as in the pharmacological and surgical treatment of patients with insulinoma.
Intranasal administration of glucagon, 1 mg, plus sodium glycocholate 15 mg as a surfactant, raised blood glucose levels and plasma levels of immunoreactive glucagon (IRG) and immunoreactive insulin (IRI). Spray solutions were more effective than drops, and neither the surfactant alone nor glucagon alone had any effect. Blood glucose levels were similarly affected by intravenous glucagon, while intramuscular glucagon was slightly more effective. The highest IRG concentrations were reached after intravenous administration, while intramuscular injection of glucagon was accompanied by the highest IRI release. These data indicate that intranasal administration of glucagon exerts metabolic effects similar to intramuscular and intravenous administrations. Further studies are needed to improve bioavailability and efficacy of intranasally administered glucagon.
In three hyperthyroid women aged more than 60 years serum TSH levels, inhibited as usual before treatment, rose and remained elevated for more than one year while on treatment with methimazole and l-thyroxine, in spite of serum T3 and T4 levels within the normal range. In two hypothyroid women aged more than 60 years, serum TSH levels, raised under basal conditions, failed to be suppressed by a one-year treatment with l-thyroxine. Repeated attempts to increase serum T3 and T4 concentrations by giving additional doses of l-thyroxine or by tapering methimazole dosage, led to clinical signs of hyperthyroidism, not accompanied by a significant reduction of serum TSH levels. These data indicate the possibility of an inappropriate TSH release in some elderly people.
Ceruletide is a synthetic decapeptide closely resembling the 8-carboxy-terminal peptide of cholecystokinin (CCK-8) with which it shares several biological properties. In a double-blind study versus placebo, we evaluated the effects of ceruletide on self-rated hunger and food intake at lunch time, as well as on body weight in 14 obese women hospitalized for weight reduction and on a restricted diet. During two 6-day courses of treatment with ceruletide or placebo, ceruletide 0.3 microgram/kg b.wt. or an equivalent volume of its diluent were injected IM at 11.30 a.m., i.e., 30 min before lunch. Feelings of hunger were quantitated, using a visual analogue self-rating scale, prior to the injection of ceruletide or placebo and 30 min thereafter, i.e., just prior to the start of meal ingestion, as well as 2 hr after the start of the meal. Duration and caloric content of food ingested at lunch, as well as morning body weight, were recorded daily. Ceruletide, compared to placebo, did not significantly influence any of the above variables. However, in the first three experimental days, the increase in self-rated hunger from values before the injection to 30 min thereafter was less marked, though not significantly so (0.05 less than p less than 0.1), with ceruletide than with placebo. Thus, it appears that ceruletide, under the experimental conditions of the present study, was not effective in enhancing the patients' motivation to lose weight and to further restrict their food intake at lunch time.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Intranasal insulin is effective in raising serum insulin (IRI) levels and lowering blood glucose levels in normal subjects and in diabetics, but its bioavailability is low. Our aim was to improve the bioavailability of intranasally administered insulin in normal subjects as a prerequisite to extended clinical trials. Solutions of regular porcine and human insulin, 40 U/ml, with sodium glycocholate 1 % w/v as a surfactant, administered in drops (0.9 U/Kg b.w.), were equally effective in terms of bioavailability and of hypoglycaemic activity. Spray solutions (0.5 U/Kg b.w.) of human insulin, 100 U/ml, were more effective than drops, and of the two surfactants employed, sodium glycocholate 4 % w/v was significantly more effective than 9-lauryl-ether and more effective than other formulations used here or described by other authors. Although being subject to further improvement, the formulation of human insulin 100 U/ml plus sodium glycocholate 4 % w/v delivered as a spray solution described in this study appears to be worthy of clinical trials in diabetic patients.