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N Passariello

Publications and source records attributed to N Passariello.

63 records · Page 4Linked to original sources

Impaired insulin secretion in human diabetes mellitus. Effect of pharmacological activation of gamma-aminobutyric acid system.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system plays a role in the defective insulin secretion in human diabetes mellitus, 15 non-insulin-dependent diabetics with fasting hyperglycemia above 140 mg/dl were submitted to two consecutive i.v. glucose tolerance tests (IVGTT) (0.33 g/kg b.w.), in basal conditions and after pharmacologic activation of the GABA system with baclofen and sodium valproate. Baclofen, a synthetic analogue, was given to 8 diabetics in two divided doses of 10 mg each 8h and 1h before the post-treatment test; sodium valproate, a drug that increases endogenous GABA activity, was given orally (800 mg) 60 min before the performance of the post-treatment IVGTT. Neither treatment brought about significant changes in insulin, C-peptide, glucagon or growth hormone responses to i.v. glucose nor did they significantly change glucose disappearance rates. These results seem to indicate that GABA does not play a major role in the pathogenesis of defective insulin secretion in non-insulin-dependent diabetes mellitus.

Aged↗

Somatostatin and insulin secretion in man. II. The effect of theophylline.

This study was aimed at evaluating the effect of theophylline, a drug that increases the intracellular concentrations of cAMP by inhibiting phosphodiesterase activity, on somatostatin (SRIF)-mediated inhibition of insulin secretion in man. Acute insulin response (AIR) to i.v. glucose (mean change 3-10 min) was almost totally suppressed by SRIF (500 micrograms/h) and glucose utilization was reduced (p less than 0.0001). These SRIF-induced decreases failed to be eliminated by a concurrent infusion of theophylline (100 mg as a loading dose followed by a constant infusion of 5 mg/min). Theophylline alone resulted in a significant increase in both AIR (p less than 0.01) and glucose removal rates (p less than 0.05). Thus, our data disprove the involvement of the phosphodiesterase enzymes in the inhibitory action of SRIF on glucose-induced insulin secretion in man.

Adult↗

Metabolic control may alter antithrombin III activity but not its plasma concentration in diabetes: a possible role for nonenzymatic glycosylation.

The effects of metabolic control on both antithrombin III (AT III) activity and AT III plasma concentration in 20 insulin-treated diabetic subjects have been evaluated. Basal AT III activity was significantly lower in diabetic subjects versus healthy controls (P less than 0.001), whereas no difference was found in AT III concentration. A good correlation was found between AT III activity and AT III concentration (r = 0.81; P less than 0.001) in healthy controls, but this correlation was not significant in diabetic subjects (r = 0.12; P = NS). In those subjects a linear inverse correlation was found to exist between AT III activity and level of glycosylated proteins (r = -0.43; P less than 0.05). Diabetic subjects were also examined after 1 and 2 mo of restored metabolic control, obtained by human insulin (DNA-recombinant) therapy. Improved metabolic control was characterized by an increase of AT III activity (P less than 0.05), a decrease of mean daily blood glucose, and stable HbA1 and glycosylated proteins (P less than 0.05), while AT III concentration did not vary. On the other hand, a significant inverse correlation between AT III activity and glycosylated proteins was found during both the first and second months (r = -0.54 and r = -0.53, respectively; P less than 0.01). Moreover, no correlation between AT III activity and AT III concentration was found. These data suggest that impaired metabolic control may alter the biologic activity of AT III in diabetes, but not its plasma concentration.

Antithrombin III↗

Lack of diabetogenic action of calcitonin in subjects affected by insulinoma.

Calcitonin has been shown to affect calcium handling within cells thus impairing insulin secretion and glucose tolerance in healthy subjects. In the present study we investigate the effects of calcitonin on basal and nutrients-induced plasma glucose and insulin levels variations in healthy subjects (n = 10) and in patients affected by islet cell tumor (n = 6). In healthy subjects calcitonin markedly decreased basal and nutrients-induced plasma insulin levels while in patients with islet cell tumor this calcitonin-mediated effect was lost. So we conclude that the lack of calcitonin effect upon insulin secretion in patients with insulinoma is probably due to the autonomous insulin secretion characterizing islet cell tumor.

Adenoma, Islet Cell↗

Role of alpha and beta cells in the impaired glucose tolerance of thalassaemic subjects.

Fifty healthy and 12 thalassaemic subjects underwent both an oral glucose tolerance test (OGTT) and arginine test in order to investigate their alpha and beta cell activity. While basal plasma levels were similar in both group of subjects (82 +/- 4 vs 74 +/- 4 mg/dl, p = NS), following glucose intake impaired glucose tolerance was observed in thalassaemic subjects. These subjects showed impaired insulin secretion either in steady-state conditions or after glucose intake. When an arginine test was performed in thalassaemic subjects, impaired insulin secretion with concomitant exaggeration of glucagon response was also observed. In the thalassaemic subjects no statistically significant correlations were found between impaired insulin secretion and iron overload. It is suggested that in thalassaemic subjects beta-cell dysfunction and alpha cell overactivity may lead to the development of diabetes mellitus.

Adolescent↗