Effect of methyl-p-tyrosine administration on gonadotropin and prolactin release in normal-cycling, postmenopausal and hyperprolactinemic women.
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Biomedical subjects
Publications and source records attributed to P Brunetti.
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Studies have been carried out in insulin-dependent diabetics of porcine Des-pheB1 insulin, which is an insulin analogue obtained by removal of the N-terminal aminoacid of the B chain. The therapeutic activity of Des-phe insulin (regular and semilinte preparations) was tested in a group of 24 insulin-dependent diabetics and compared with the unmodified parent compound. Both types of insulin, Des-phe and unmodified were chromatographically purified preparations. The mean daily blood glucose profile obtained with Des-phe insulin was slightly higher than that of unmodified preparations, while the mean blood glucose and the "M" index of Schlichtkrull were similar. The biological activity of regular Des-phe and its unmodified parent compound was evaluated in 6 further insulin-dependent diabetics, with the aid of an artificial endocrine pancreas. The insulin requirement to achieve an optimal metabolic control was 10% less with Des-phe insulin than with the unmodified preparation. The immunogenicity of Des-phe and unmodified insulins, tested by measuring plasma insulin antibody titres in diabetic patients either newly or already insulin treated, was comparable. However the binding capacity of 125I-Des-phe insulin to preexisting antibodies seemed to be less than that of unmodified 125I-insulin in patients previously treated with unmodified insulin. Finally Des-phe appeared able to correct promptly and completely the insulin-induced lipodystrophy of three insulin-dependent diabetics.
In order to verify whether or not insulin-induced blood glucose control can acutely lower glycosylated haemoglobin levels, HbAI (a+b+c) (HbAI) was measured in 11 diabetics before, during and after 3 days of treatment with an "artificial endocrine pancreas" (Biostator). Initially 5 patients were in fair glycaemic control (group A), while the other 6 showed poor control (group B). HbAI levels decreased significantly after 3 days in both groups A (from 9.6 +/- 0.2% to 8.5 +/- 0.3%, mean +/- SEM, p less than 0.05) and B (from 13.7 +/- 0.2% to 12.6 +/- 0.3%, p less than 0.05). A further HbAI decrease was observed until day 60 following Biostator treatment, during which period glycaemic control improved, as assessed by fasting and post-lunch plasma glucose values and daily glycosuria determined every 10 days. These results suggest that increased HbAI levels may be reversed early by strict blood glucose control during a 3 day period. It is concluded that HbAI levels not only reflect long-term glycaemic control, but also recent acute variations in mean blood glucose values.
HbA1(a+b+c)(HbA1) was determined chromatographically in 107 subjects with normal fasting plasma glucose (FPG) and 112 patients with overt diabetes. Subjects with normal FPG were divided into two groups based on their response to two oral glucose tolerance tests (OGTTs), at an interval of 2 mo. In 40 subjects with normal OGTT (group I), HbA1 ranged from 5.2% to 7.2%, while in 67 subjects with abnormal OGTT (group II), it ranged from 6.3% to 9.6%. HbA1 levels were significantly higher in group II than in group I (7.7 +/- 0.09% versus 6.4 +/- 0.08%, mean +/- SEM, P less than 0.0005), but 14 subjects of group II had HbA1 levels less than 7.2%. No correlation was found between HbA1 and FPG, OGTT peak, and curve area in either group. However, the correlation became significant in all 107 subjects with normal FPG (groups I + II). In patients with overt diabetes, HbA1 ranged from 6.3% to 18% (11.9 +/- 0.22%) and correlated with FPG (r = 0.78, P less than 0.0005). The traditional OGTT seems more sensitive than the HbA1 measurement in detecting subjects with reduced carbohydrate tolerance. HbA1 level, on the other hand, is known to be more specific indicator of structural abnormalities following long-term hyperglycemia. Thus HbA1 determination might be a helpful test along with OGTT to improve both selection and follow-up subjects with true borderline diabetes.
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Urinary excretion and plasma levels of catecholamines were determined in 20 normal and 39 diabetic subjects to evaluate the sympathetic activity. Diabetic patients were divided into 4 groups according to the metabolic control. Sympathetic activity showed no differences between normal and subjects with chemical diabetes (group I, n = 5). In insulin-treated diabetics in good metabolic control (group II, n = 11) only urinary excretion of free norepinephrine was significantly higher than normals (p less than .05). In insulin-treated diabetics in poor metabolic control (group III, n = 16) urinary excretion and plasma levels of norepinephrine showed a marked increase over groups I and II (p less than .001). In insulin-treated diabetics with ketosis (group IV, n = 7) urinary excretion and plasma levels of both norepinephrine and epinephrine showed the highest values (p less than .001 and less than .1). Finally, in groups III and IV, after achieving improved metabolic control, a significant decrease of urinary excretion and plasma levels of catecholamines was observed. The results confirm that there is an increased rate of catecholamine release in poorly controlled diabeties and suggest a close correlation between sympathetic activity and metabolic derangement in diabetes.
With the aid of an artificial beta-cell (Biostator, Miles Laboratories Inc.), a different metabolic and biological pattern of behaviour was observed in benign versus malignant insulinoma. In the patient with beta-cell adenoma but not in the one with carcinoma, plasma insulin concentrations decreased promptly and markedly, and blood glucose increased during diazoxide and somatostatin infusion. Moreover, only in the adenoma patient was glucose need characterized by a circadian rhythm with the maximum values during daytime. This behavior could reflect the degree of tumor beta-cell differentiation. The controlled glucose and insulin infusion was of great help during and after surgical treatment.
An artificial beta-cell (Biostator) was used to control blood glucose concentration in six insulin-dependent diabetics who underwent surgical procedures and in five diabetic women during both vaginal childbirth and Caesarian section. In all cases, an optimal glycometabolic control was achieved before, during, and after surgery and delivery.
Five insulin-dependent diabetics with poor metabolic control were examined at the beginning and after a three-day application of artificial endocrine pancreas (AEP). Pancreatic alpha cell function evaluated by arginine infusion (0.5 g/Kg b.w. over 30 minutes) showed no significant differences between the beginning and during artificial beta cell aplication, but the increment in plasma glucagon level over basal values observed in both tests appeared significantly higher at 30 and 60 min in comparison with a control group. Growth hormone response to arginine infusion was clearly reduced in the second test. C-peptide concentration appeared very low in basal conditions and during arginine infusion; no improvement was observed after three days of AEP application. Urinary excretion of norepinephrine markedly increased at the beginning of the study, reversed almost to normal during AEP treatment, while minor changes were observed in urinary excretion of epinephrine. The Concentration of glycosylated hemoglobin, markedly higher than normally before the connection with AEP, showed a slight but significant decrease during glucose-controlled insulin infusion. Finally, 2,3-diphosphoglycerate was normal and no modifications were observed in the course of the study.
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