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G Pozza

Publications and source records attributed to G Pozza.

At least 181 records · Page 10Linked to original sources
PubMed1990

Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome.

Stiff-man syndrome is a rare disorder of the central nervous system of unknown pathogenesis. We have previously reported the presence of autoantibodies against glutamic acid decarboxylase (GAD) in a patient with stiff-man syndrome, epilepsy, and insulin-dependent diabetes mellitus. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) and in pancreatic beta cells. We subsequently observed autoantibodies to GABA-ergic neurons in 20 of 33 patients with stiff-man syndrome. GAD was the principal autoantigen. In the group of patients positive for autoantibodies against GABA-ergic neurons, there was a striking association with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus. These findings support the hypothesis that stiff-man syndrome is an autoimmune disease and suggest that GAD is the primary autoantigen involved in stiff-man syndrome and the associated insulin-dependent diabetes mellitus. Our findings also indicate that autoantibodies directed against GABA-ergic neurons are a useful marker in the diagnosis of the disease.

Autoantibodies↗
PubMed1990

Reduction of insulin resistance by combined kidney-pancreas transplantation in type 1 (insulin-dependent) diabetic patients.

To evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy. 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisone-treated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that short-term (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance.

Adult↗
PubMed1990

Effect of acipimox, a lipid lowering drug, on growth hormone (GH) response to GH-releasing hormone in normal subjects.

Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GH-releasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 micrograms iv The GH response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH.

Adult↗
PubMed1990

The glucose clamp technique for the study of patients with hypoglycemia: insulin resistance as a feature of insulinoma.

Occurrence of hypoglycemia during a prolonged fasting, accompanied by inappropriately high serum insulin levels, is considered a reliable index of the presence of insulinoma. Previous in vitro studies on insulin receptors, and in vivo hyperinsulinemic clamps have shown that patients with insulinoma are insulin resistant. In the present study 10 patients with insulinoma, 6 patients with nontumoral (also called functional or reactive hypoglycemia) hypoglycemia and 6 normal subjects were fasted for 24 h and their blood glucose levels were maintained constant by means of a programmed glucose infusion (isoglycemic glucose clamp) delivered by an artificial pancreas (Biostator). Blood glucose levels were monitored in continum, glucose infused (M) and glucose clearance (MCR) were evaluated at hourly intervals, and serum insulin (IRI) levels were evaluated every 6 h. Blood glucose levels were higher in controls than in patients with insulinoma and in patients with non tumoral hypoglycemia; M, MCR and IRI were progressively higher in controls, in patients with nontumoral hypoglycemia and in patients with insulinoma. The M/I index (M divided by IRI levels, an index of insulin sensitivity) was lower in patients with insulinoma than in other subjects and patients, indicating the existence of insulin resistance. These data indicate that: i) patients with insulinoma require large amounts of glucose to remain isoglycemic during a prolonged fast; ii) insulin resistance is a common feature of insulinoma and can be shown even under near physiologic conditions such as a 24-h fasting. The present study does not clarify whether insulin resistance occurs at the hepatic level or at other, peripheral levels.

Adolescent↗
PubMed1990

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes.

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.

Adult↗
PubMed1990

The growth hormone clamp technique: inhibition of growth hormone release by growth hormone occurs independently of free fatty acids.

It has been suggested that growth hormone (GH) can inhibit its own release: in fact it has repeatedly been shown that an acute methionyl-GH (met-GH) infusion blocks the GH response to GH-releasing hormone (GHRH). However, met-GH infusions are accompanied by a significant increase of free fatty acids (FFA), which can block GH release. The aim of this study was to evaluate whether the inhibition of GH response to GHRH also occurs when lipolysis is pharmacologically blocked. Therefore, six normal subjects received GHRH, 50 micrograms intravenously (IV), after a 4-hour saline infusion and a 4-hour met-GH infusion (80 ng/kg/min, yielding a constant GH level of 33.6 +/- 4.63 micrograms/L), and GH release was evaluated during the following 2 hours. To prevent lipolysis, all subjects received on both occasions acipimox, an antilipolytic agent, 500 mg during the 6 hours before IV GHRH. GHRH induced a clear GH release during saline infusion (46.6 +/- 2.70 micrograms/L) and a scanty GH release during met-GH infusion (9.3 +/- 1.52 micrograms/L; P less than .01). Plasma levels of FFA, somatostatin, insulin-like growth factor I (IGF-I), and glucagon and serum insulin levels were unaffected, while blood glucose levels slightly decreased during saline infusion, but not during GH infusion. These data confirm that met-GH inhibits GHRH-induced GH release, and demonstrate that this inhibition is not mediated by FFA levels.

Adult↗
PubMed1990

Prednisone administration in recent onset type I diabetes.

The aim of our study was to investigate the efficacy of prednisone to preserve pancreatic beta-cell function in patients with recent-onset Type I diabetes mellitus (IDDM). Twenty-five patients with IDDM, aged 24 +/- 6 years, entered the trial within 8 weeks of the onset of diabetes. They were allocated, according to a single blind randomized protocol, to one of the following treatments: (A) prednisone (15 mg/day), (B) indomethacin (100 mg/day), (C) placebo. All treatments lasted 8 months and all patients achieved satisfactory metabolic control with a multi-injection regimen (three injections/day) within a few weeks, and maintained it throughout the entire period of observation. Only minor side effects were observed in the prednisone-treated patients. A lower insulin requirement was observed in the prednisone group than in other patients at 12 months (0.33 +/- 0.11 vs 0.57 +/- 0.06 U/kg/day, P less than 0.05), 18 months (0.34 +/- 0.11 vs 0.64 +/- 0.06, P less than 0.05) and 24 months (0.38 +/- 0.10 vs 0.63 +/- 0.05, P less than 0.05). Endogenous insulin release, evaluated as urinary C-peptide, was higher in the prednisone group than in other patients at 3, 6, 9, 12, 18 and 24 months (P less than 0.05). ANOVA confirmed differences among the three groups. Our study indicates that prednisone administration, at low doses and for a long period of time, effectively restored endogenous insulin release in IDDM patients.

Adolescent↗
PubMed1990

Basal and norepinephrine-stimulated lipolysis in differently sized human isolated adipocytes: comparison of three modalities for results expression.

Lipolytic rate in basal conditions and after adrenergic stimulation with norepinephrine (NE, 8.87 microM) from suspensions of differently sized human adipocytes has been tested. Adipocytes were intra surgically provide for obese (OB) and normal-weight (NW) individuals. Total volume of cells was constant in all samples, being 4% in the incubation system. Glycerol released in the buffer at the end of one hour incubation was measured and results expressed by three different features, i.e. related to: A) total volume of cells (nmol glycerol/40 microliters/h); B) cell number (nmol/cell x 10(4)/h), or C) cell surface unit (nmol/mm2/h). No statistically significant differences between OB and NW have been found, nor between histometrical parameters or between lipolytic rates. A positive, significant correlation between lipolytic rate B and Mean Cell Volume (MCV) or total Cell Surface (TCS 10(4)) has been found (rs from 0.90 to 0.94, p less than 0.01) both in basal conditions and after stimulation. A significant, positive correlation between stimulated lipolytic rate C and MCV (r = 0.67, p less than 0.05) has also been observed. Our results suggest that lipolytic rate appears to be correlated to cell volume. While the expression of lipolytic rate with relation to total volume of cells in the sample (rate A) may be more convenient to minimize the effect of different size of cells in different samples, data expressed as glycerol released per number of cells (rate B) or per surface unit (rate C) appears however to be more suitable form main experimental purposes in metabolic studies of adipocytes.

Adipose Tissue↗
PubMed1990

Swine islet isolation and transplantation.

An isolation procedure for large scale isolation of swine islets is described. The results from 15 consecutive isolations are reported. The glands were excised from heart beating animals with no warm ischemia time. The pancreases were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets for gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80-95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 after purification. After transplantation of an aliquot of the final preparation in diabetic nude mice normoglycemia occurred in six mice. 30 days after transplantation nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases.

Animals↗
PubMed1990

Selection of donors significantly improves pig islet isolation yield.

The purpose of the present study was to test the influence of donor age on islet isolation yield in swines. Large White pigs of 10 months (group 1, n = 10) and 2-3 years (group 2, n = 5) were used. A modification of the automated method for human islet isolation was used for pig islet separation. After ductal injection of a collagenase solution (Seromed, type C-1000) the islets were separated through a continuous digestion process. In group 1 it was possible to obtain an average of 636,100 islets (volume = 476.1 mm3, insulin content = 101.4 Units). In group 2 the average total islet number was 799,800 representing a volume of 1190.6 mm3 (Insulin content 210 Units). Total islet number was not significantly different in the two groups, however when islet volume and total insulin content were considered, older animals allowed a significantly higher yield (P less than 0.01 for volume and P less than 0.05 for insulin content). These findings indicate that it is possible to separate large number of pig islets from both young (10 months) and older (2-3 years) animals and that selection of donor pigs will improve islet isolation yield. These results may be of assistance in the definition of requirements for more effective islet isolation in swines.

Animals↗
PubMed1990

Isolation of the elusive pig islet.

This study describes a procedure for large scale isolation of swine islets. The reported results are from 15 consecutive isolations. The glands were removed from live animals with no warm ischemia, and the pancreata were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets per gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80% to 95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 U after purification. After a 10 mm3 aliquot of the final preparation was transplanted under the renal subcapsular space of seven nude mice with diabetes, normoglycemia occurred in six of the mice. Thirty days after transplantation, nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases. This method makes it possible to provide large numbers of intact swine islets for preliminary studies of prevention of the rejection of pig islet xenograft by immunoalteration and immunoisolation procedures.

Animals↗