Showing papers by "Giuseppe Paolisso published in 1992"

ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients.

Abstract: We have compared the cardiovascular and metabolic responses to five different ACE inhibitors in 86 patients matched for age, body mass index, blood pressure, fasting plasma glucose and insulin levels in a placebo-controlled, double-blind, crossover, randomised trial. In the active drug treatment phase the patients were randomly assigned to one of five ACE inhibitors: captopril (75 mg/day; n = 16); enalapril (20 mg/day; n = 14); quinapril (20 mg/day; n = 17); ramipril (5 mg/day; n = 21) and lisinopril (20 mg/day; n = 18). Placebo and ACE inhibition phases lasted two weeks and were separated by a one week wash-out period. At the end of each treatment period blood pressure and heart rate were recorded and a fasting sample intravenous glucose tolerance test was conducted. Our study demonstrated that ACE inhibition significantly reduces blood pressure and improves insulin sensitivity. All the ACE inhibitors studied had similar cardiovascular responses but lisinopril displayed the larger metabolic response.

Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin-dependent diabetics.

Abstract: In healthy subjects (n = 10) and non-insulin-dependent (type II) diabetics (n = 10) matched for age [43.1 +/- 2.2 vs. 41 +/- 4.4 yr, P = not significant (NS)], body mass index (25.1 +/- 1.1 vs. 26 +/- 0.8 kg/m2, P = NS), gender ratio [5 males (M)/5 females (F) vs. 5M/5F], and mean arterial blood pressure (105 +/- 7 vs. 106 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after glutathione infusion (15 mg/min) and the relative increase in the plasma reduced (GSH)/oxidized (GSSG) glutathione ratio. The rise in the plasma GSH/GSSG ratio significantly improved total body glucose disposal in healthy subjects and in diabetic patients. In this latter group, GSH infusion potentiated the beta-cell response to glucose slightly. In controls and diabetics, insulin infusion with a simultaneous increase in the plasma GSH/GSSG ratio significantly enhanced nonoxidative glucose disposal without affecting oxidative glucose metabolism. After glutathione infusion, all metabolic and hormonal changes correlated with a significant decline in plasma membrane microviscosity. In conclusion, the plasma GSH/GSSG ratio seems to play a major role in the modulation of glucose homeostasis mainly in diabetics.

Glutathione Infusion Potentiates Glucose-Induced Insulin Secretion in Aged Patients With Impaired Glucose Tolerance

Abstract: Objective –To evaluate the effect of glutathione infusion on β-cell response to glucose in elderly people with impaired glucose tolerance (IGT). Research Desigh and Methods –Ten patients with normal glucose tol-erance and 10 patients with IGT were matched for age (mean ± SE, 72.1 ± 2.8 vs. 71.0 ± 3.4 yr), body mass index (23.1 ± 1.1 vs. 22 ± 2.1 kg/m 2 ), and sex (6/4 vs. 5/5, men/women) underwent glutathione infusion (10 mg/min) under basal conditions and during 75-g oral glucose tolerance tests and intravenous glucose tolerance tests (0.33 g.kg body wt −1 .3 min −1 ). Patients with IGT were also submitted to euglycemic-hyperinsulemic and hyperglycemic glucose clamps. Results –In subjects with normal glucose tolerance, glutathione infusion failed to affect β-cell response to glucose. In contrast, glutathione significantly potentiated glucose-induced insulin secretion in patients with IGT. Furthermore, in the latter group studied by hyperglycemic clamps, glutathione infusion significantly potentiated the beta-cell response to glucose when plasma glucose levels varied between 10 and 15 mM. This effect disappeared at plasma glucose levels Conclusios –Glutathione infusion enhances insulin secretion in elderly people with IGT.

Hyperinsulinemia in patients with hypercholesterolemia.

Abstract: An independent association between hypercholesterolemia and high insulin levels has not consistently emerged from large-scale epidemiologic observations. We selected 39 patients with elevated low-density (LDL) cholesterol levels but normal body weight, blood pressure, and glucose tolerance, and compared them to 36 normocholesterolemic, healthy control subjects accurately matched to the patients for age, gender, body mass index, and mean arterial blood pressure. Fasting serum total cholesterol concentrations and levels of LDL cholesterol, triglycerides, and apoprotein B were all higher in the patients with hypercholesterolemia than in controls (P < 0.025 or less), whereas high-density lipoprotein cholesterol and apoprotein A levels were significantly lower (P < 0.05 or less). Plasma insulin concentrations were elevated in hypercholesterolemic patients vs. controls both in the fasting state (86 +/- 6 vs. 59 +/- 8 pmol/L) and 2 h after a 75-g oral glucose load (412 +/- 16 vs. 276 +/- 18 pmol/L, P < 0.02 for ...

Insulin effects on glucose kinetics in non-insulin-dependent diabetic patients with secondary failure to hypoglycaemic agents: role of different modes and rates of delivery.

Abstract: OBJECTIVES This study aimed at investigating the effects of pulsatile and continuous insulin delivery on glucose kinetics in non-insulin-dependent (type 2) diabetic patients with secondary failure to oral hypoglycaemic agents. METHODS Seven type 2 diabetic patients underwent a 585 minute glucose-controlled glucose intravenous infusion using the Biostator. The endogenous pancreas secretion was inhibited by somatostatin. Three experiments were performed in each patient on different days and in random order. In all cases, glucagon was replaced (58 ng/min). The amounts of insulin infused were: a) 0.15 mU/kg x min continuously; b) 0.20 mU/kg x min continuously and c) 1.0 mU/kg x min in 2 minute pulses every 13 minutes. D-[3-3H]-glucose infusion allowed determination of glucose kinetics. RESULTS Infusion of identical amounts of insulin (A vs C) demonstrated that pulsatile insulin delivery exerted greater metabolic effects (higher glucose infusion rate and, mainly at the beginning of the experiment, lower endogenous glucose production) than continuous infusion; furthermore pulsatile insulin delivery (C) exerted metabolic effects similar to those of a greater dose of insulin (B) infused continuously. CONCLUSIONS In type 2 diabetic patients with secondary failure to oral hypoglycaemic agents, pulsatile insulin delivery exerts greater metabolic effects than continuous hormone delivery.

Effects of mild-to-moderate hyperglycaemia per se on glucose production and uptake in the elderly.

Abstract: OBJECTIVES In order to better understand the mechanisms responsible for the diminished glucose tolerance that occurs in the elderly, the present study aimed at investigating the effect of mild hyperglycaemia on glucose production and uptake in a group of aged subjects. For comparison, a group of young subjects was simultaneously investigated. METHODS Seven aged (71.8 +/- 2.3 yrs) and seven young (25.5 +/- 1.7 yrs) healthy non-obese subjects underwent two hyperglycaemic glucose-clamps having as targets plasma glucose levels 7.5 and 10.0 mmol/L. Contemporary infusion of D-[3-3H]-glucose allowed determination of glucose turnover parameters in basal conditions and during the clamps. Endogenous pancreatic secretion was inhibited by somatostatin (8.3 micrograms/min) while glucagon (67 ng/min) and insulin (0.15 mU/kg/min) were replaced by exogenous infusions. RESULTS In basal conditions, glucose uptake (12.9 +/- 0.5 vs 14.4 +/- 0.4 mumol/kg/min; p < 0.05) and glucose metabolic clearance rate (2.58 +/- 0.15 vs 3.35 +/- 0.10 ml/kg/min; p < 0.01) were lower in elderly vs young subjects. In the hyperglycaemic glucose-clamps, we observed, in the elderly subjects, the persistence of a greater glucose production during mild (7.5 mmol/L) (11.6 +/- 0.4 vs 9.7 +/- 0.2 mumol/kg/min; p < 0.005) but not moderate (10 mmol/L) (3.5 +/- 0.1 vs 3.4 +/- 0.1 mumol/kg/min; NS) hyperglycaemia. In contrast, glucose-induced glucose uptake and glucose metabolic clearance rate were similarly affected by glucose infusions in both groups of subjects. Moreover, in elderly but not in young subjects, basal glucose disappearance rate was significantly negatively correlated with fasting plasma glucose levels (r = -0.84; p < 0.01). CONCLUSIONS In the basal state, glucose uptake and glucose metabolic clearance rate are slightly impaired in elderly, compared to young subjects. Furthermore, in the elderly, endogenous glucose production is less suppressed by mild hyperglycaemia i.e. 7.5 mmol/L, than it is in young people. Such impairment in the inhibition of endogenous glucose production is not seen when blood glucose attains 10 mmol/L. We suggest that impairment in glucose tolerance in the elderly results from both reduced glucose uptake (in basal conditions) and excessive glucose production (at mild hyperglycaemic levels).