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Biomedical subjects

G Paolisso

Publications and source records attributed to G Paolisso.

At least 109 records · Page 6Linked to original sources
PubMed1995

Left ventricular hypertrophy is associated with a stronger impairment of non-oxidative glucose metabolism in hypertensive patients.

Hypertensive patients with left ventricular hypertrophy (LVH) have a higher degree of hyperinsulinaemia than hypertensive patients without LVH. Obese patients with LVH have also been demonstrated to have a very low glucose disappearance rate after an intravenous glucose bolus. No studies have investigated the difference in insulin action and substrate oxidation in hypertensive patients with and without LVH. For this reason 36 subjects were enrolled for our study: (1) healthy control subjects (n = 10); (2) hypertensive patients without LVH (n = 12); and (3) hypertensive patients with LVH (n = 14). All subjects underwent an oral glucose tolerance test (OGTT, 75 g of glucose) and a euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate, 7.1 pmol (kg min)-1 for 120 min). In this latter test indirect calorimetry allowed substrate oxidation determination. Echocardiographic methods allowed LVH assessment. Hypertensive patients with LVH had the lowest insulin-mediated nonoxidative glucose metabolism compared to hypertensive patients without LVH (P < 0.01) and to healthy subjects (P < 0.001). In the whole group of hypertensive patients (n = 26), partial correlations showed left ventricular mass index (LVMI) associated with fasting plasma insulin levels (r = 0.44 P < 0.005), insulin-mediated whole body glucose disposal (r = -0.41 P < 0.01) and nonoxidative glucose metabolism (r = -0.33 P < 0.04) independently of age, body weight, systolic blood pressure and plasma catecholamines levels. In conclusion, our data provide evidence that LVH in hypertensive patients is associated with a worsening in nonoxidative glucose metabolism.

Blood Glucose↗
PubMed1995

Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects.

The present study aimed at evaluating whether acute elevations of plasma glucose concentrations could influence systemic hemodynamic parameters and baroreflex activity in humans. Plasma glucose concentrations were acutely raised to 15 mmol/l in 12 healthy male volunteers. During hyperglycemia, there were significant increments of systolic [from 118 +/- 9 to 138 +/- 12 (SD) mmHg, P < 0.01] and diastolic (from 71 +/- 5 to 85 +/- 6 mmHg, P < 0.001) blood pressure, as well as heart rate (from 76 +/- 7 to 85 +/- 10 beats/min, P < 0.01) and plasma catecholamine levels. Both maximal and steady-state mean arterial pressure after squatting were higher during hyperglycemia (27 +/- 8 and 16 +/- 6 mmHg, respectively) compared with levels obtained during euglycemia (18 +/- 5 and 2 +/- 0.6 mmHg, respectively, P < 0.001). The infusion of the somatostatin analogue octreotide (25 micrograms as i.v. bolus followed by a 0.5 microgram/min infusion), to avoid the possible confounding vascular actions of insulin, did not influence the hemodynamic effects of hyperglycemia except for a lesser increase of both heart rate and plasma catecholamines. Glutathione (600 mg as an iv bolus followed by a 5 mg/min infusion) completely prevented the vascular effects of hyperglycemia. This study shows that acute hyperglycemia, similar to that observed in poorly controlled diabetic patients, produces relevant systemic hemodynamic changes and also alters baroreflex activity via a glutathione-sensitive presumably free radical-mediated pathway.

Adult↗
PubMed1995

Glucose handling, diabetes and ageing.

The relationship between ageing and glucose homeostasis is still an open debate. In fact, the mechanisms by which glucose metabolism is progressively impaired with increasing age are not completely understood. In the present report we have reviewed the possible mechanisms (impaired insulin secretion and action, role of the environmental factors) which may lead to the impairment in glucose handling associated with ageing. We also point out that not all aged subjects are glucose intolerant; in fact, it has been suggested that only those aged subjects who present more than one pathological finding do in fact develop impaired glucose handling.

Aging↗
PubMed1995

An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action.

Adult↗
PubMed1995

Intracellular magnesium and insulin resistance: results in Pima Indians and Caucasians.

Intracellular magnesium is a cofactor for numerous enzymes involved in carbohydrate metabolism. Magnesium accumulation is dependent upon insulin action and correlates with insulin-mediated glucose uptake. As Pima Indians are known to be insulin resistant, we investigated whether, in response to insulin infusion, they have lower erythrocyte magnesium accumulation than Caucasians. Insulin-mediated glucose uptake was determined by a euglycemic hyperinsulinemic glucose clamp in 29 obese nondiabetic volunteers: 15 Caucasians (8 males and 7 females) and 14 Pima Indians (8 males and 6 females). Pima Indians were younger than Caucasians (mean +/- SD, 28 +/- 7 vs. 39 +/- 8 yr; P < 0.01), but had similar body mass index and fasting/2-h plasma glucose concentrations. Despite higher steady state plasma insulin levels (692 +/- 260 vs. 540 +/- 70 pmol/L; P < 0.03), Pima Indians had lower insulin-mediated glucose uptake than Caucasians (108 +/- 20 vs. 244 +/- 32 mg/m2.min; P < 0.0001). The mean fasting plasma magnesium concentration was lower in Pima Indians than in Caucasians (0.79 +/- 0.05 vs. 0.85 +/- 0.06 mmol/L; P < 0.01), whereas the mean fasting erythrocyte magnesium concentrations (1.98 +/- 0.10 vs. 2.03 +/- 0.14 mmol/L) were similar in the 2 groups. In response to insulin infusion, erythrocyte magnesium content increased less in Pima Indians than in Caucasians (0.15 +/- 0.07 vs. 0.28 +/- 0.21 mmol/L; P < 0.03). However, this increase was similar in the 2 groups when values were adjusted for insulin-mediated glucose uptake. In conclusion, nondiabetic Pima Indians have a lower erythrocyte magnesium accumulation in response to insulin infusion; this is probably due to their high degree of insulin resistance. The biochemical and physiological consequences of decreased intracellular magnesium uptake are discussed.

Adult↗
PubMed1995

Low-dose iloprost infusion improves insulin action in aged healthy subjects and NIDDM patients.

OBJECTIVE: To investigate the effect of iloprost infusion on insulin action. RESEARCH DESIGN AND METHODS: Thirteen healthy subjects and 13 non-insulin-dependent diabetes mellitus (NIDDM) patients matched for age (68.2 +/- 0.5 vs. 67.9 +/- 0.5 years, NS), gender ratio (7 men:6 women vs. 6 men:7 women), body weight, body fat distribution, arterial blood pressure, and plasma triglyceride levels (1.89 +/- 0.09 vs. 1.87 +/- 0.08 mmol/l, NS) were studied. In eight healthy subjects and eight NIDDM patients, we studied insulin action by euglycemic glucose clamp (insulin infusion rate 2 mU.kg-1.min-1) along with saline and iloprost delivery (0.7 ng.kg-1.min-1). In the other five subjects of each group, forearm blood flow and insulin-mediated glucose uptake during saline and iloprost infusion (0.7 ng.kg-1.min-1) were investigated. RESULTS: Iloprost infusion improved insulin-stimulated whole-body glucose uptake and oxidative and nonoxidative glucose metabolism in both study groups. Forearm blood flow under basal conditions and with insulin infusion (2 mU.kg-1.min-1) did not show any significant difference from that during saline and iloprost infusion (0.7 ng.kg-1.min-1) in healthy subjects and diabetic patients. CONCLUSIONS: Iloprost infusion improves insulin action in healthy subjects and NIDDM patients.

Aged↗
PubMed1995

Lisinopril administration improves insulin action in aged patients with hypertension.

Thirty elderly, mildly hypertensive patients were enrolled for a single-blind, randomised cross-over placebo controlled trial in which placebo and lisinopril (20 mg/day before breakfast) were given for 4 and 8 weeks, respectively. A wash-out period of 3 weeks between placebo and lisinopril was observed. In each patient a euglycaemic glucose clamp with simultaneous indirect calorimetry allowed us to determine whole body glucose disposal and substrate oxidation. Changes in morning SBP and DBP were also determined. Lisinopril vs. placebo significantly improved whole body glucose disposal (40.4 +/- 0.4 vs. 30.3 +/- 0.4 mumol/kg LBM x min; P < 0.01), non-oxidative glucose metabolism (18.1 +/- 0.7 vs. 10.9 +/- 0.6 mumol/kg LBM x min; P < 0.01) and fasting plasma potassium levels (4.8 +/- 3 vs. 4.4 +/- 0.4 mmol/l; P < 0.05). SBP (175 +/- 3.3 vs. 160 +/- 3.0 mm Hg; P < 0.001) and DBP (106 +/- 2.3 vs. 95 +/- 2.0 mm Hg; P < 0.001) were significantly reduced by lisinopril administration. After ACE inhibition, fasting plasma potassium levels correlated with the decline in mean arterial BP (r = -0.71; P < 0.006). In conclusion, lisinopril administration reduces arterial BP and improves insulin sensitivity in elderly hypertensive patients.

Aged↗
PubMed1995

Low fasting and insulin-mediated intracellular magnesium accumulation in hypertensive patients with left ventricular hypertrophy: role of insulin resistance.

Twenty-five hypertensive patients (13 males/12 females) with left ventricular hypertrophy (LVH) and 12 hypertensive patients (6 males/6 females) without LVH were studied. Both groups were matched for age, sex, body mass index, percentage body fat, arterial BP and known duration of hypertension. After a seven day wash-out period from antihypertensive treatment each subject underwent: (1) an oral glucose tolerance test, (2) an euglycemic hyperinsulinaemic glucose clamp (insulin infusion rate 7.1 pM/kg per min), (3) an echocardiographic determination of left ventricular mass index, and (4) 24h ECG Holter monitoring. All tests were performed in random order and on different days. All investigators were unaware of the patient groups. Hypertensive patients with LVH had lower fasting intracellular (erythrocyte) magnesium concentrations (1.85 +/- 0.06 vs. 2.07 +/- 0.04 mM; P < 0.001) but higher fasting plasma insulin concentrations (86 +/- 4 vs. 59 +/- 5 pM; P < 0.001) Glucose clamp study demonstrated a lower insulin-mediated glucose disposal (24.8 +/- 0.4 vs. 30.1 +/- 0.3 microM/kg of lean body mass per min; P < 0.05) and a net change in intracellular magnesium accumulation (17.9 +/- 1.3 vs. 27.3 +/- 1.8%, P < 0.01) in response to insulin infusion in hypertensive patients with LVH than in those without LVH. After adjustment for fasting plasma insulin levels and insulin-mediated glucose uptake, fasting and insulin-mediated erythrocyte magnesium accumulation were no longer different between the two groups. In conclusion, hypertensive patients with LVH compared with those without LVH have a lower intracellular magnesium content due a higher degree of insulin resistance.

Double-Blind Method↗
PubMed1995

Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.

Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weight, arguing for acquired rather than inherited metabolic defects in presence of morbid obesity. If a sufficient weight reduction can not be obtained, pharmacological approaches may be considered to improve insulin resistance of obese subjects, especially those with impaired glucose tolerance or overt diabetes.

Blood Glucose↗
PubMed1994

Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic patients.

Ten healthy subjects and 30 non-insulin-dependent (type II) diabetic patients matched for age, gender ratio, body mass index, lean body mass (LBM), waist to hip ratio, and arterial blood pressure volunteered for the study. In all subjects, fasting plasma free radical (O2-) levels and basal membrane lipid fluidity (MLF) and protein mobility (MPM) were determined. The whole group of subjects underwent a euglycemic hyperinsulinemic glucose clamp with simultaneous indirect calorimetry for substrate oxidation determination. Diabetic patients versus controls displayed higher fasting plasma glucose (8.3 +/- 0.4 v 5.1 +/- 0.4 mmol/L, P +/- .001), O2- (0.48 +/- 0.02 v 0.16 +/- 0.02 mumol/L x min), and hemoglobin A1c ([HbA1C] 7.9% +/- 0.4% v 5.7% +/- 0.3%, P < .03) levels and a stronger reduction in basal MLF (0.243 +/- 0.006 v 0.318 +/- 0.009, P < .003) and basal MPM (0.348 +/- 0.003 v 0.518 +/- 0.010, P < .002). Whole-body glucose disposal (WBGD) and oxidative and nonoxidative glucose metabolism were also significantly lower in diabetics than in controls. In diabetic patients (n = 30), plasma O2- levels correlated with basal MLF (r = -.59, P < .005), basal MPM (r = -.84, P < .001), fasting plasma insulin level (r = .51, P < .004), WBGD (r = -.53, P < .002), and nonoxidative (r = -.45, P < .01) glucose metabolism. In conclusion, our results demonstrate that a relationship between plasma O2- levels and insulin action occurs in non-insulin-dependent diabetics.

Aged↗
PubMed1994

Total-body and myocardial substrate oxidation in congestive heart failure.

Congestive heart failure is a condition associated with increased plasma norepinephrine levels, which have been demonstrated to impair glucose handling. In the present study, 10 patients suffering from congestive heart failure and 10 healthy age- and body mass index-matched subjects were submitted to a hyperinsulinemic (insulin infusion rate, 0.5 mU/kg.min-1) glucose clamp, while simultaneous D-3H-glucose infusion and indirect calorimetry allowed for determination of glucose turnover parameters and substrate oxidation, respectively. On a separate day, basal local (myocardial) indirect calorimetry was also performed. Our data demonstrate that in congestive heart failure, fasting myocardial glucose oxidation (Gox) was inhibited with a simultaneous increase in lipid oxidation (Lox). In our patients, a significant decrease in total-body insulin-stimulated glucose metabolism (31.0 +/- 0.5 v 20.3 +/- 0.4 mumol/kg.min-1, P < .01) and nonoxidative glucose metabolism (18.9 +/- 1.1 v 11.0 +/- 0.5 mumol/kg.min-1, P < .05) was also found. Such latter changes were also associated with a simultaneous overdrive of Lox (0.4 +/- 0.2 v 1.9 +/- 0.2 mumol/kg.min-1, P < .02) that was correlated with an enhanced availability of plasma free fatty acids (FFAs).

Aged↗
PubMed1994

Pharmacological doses of vitamin E and insulin action in elderly subjects.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

Aged↗
PubMed1994

Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics.

In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10) subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after vitamin C infusion and the relative increase in plasma vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the increase in plasma vitamin C levels did not affect B cell response to glucose, but it improved Conard's K values and whole body glucose disposal in healthy subjects and in diabetic patients. In both groups of subjects vitamin C-mediated increase in insulin action was mainly due to an improvement in nonoxidative glucose metabolism. After fasting, plasma vitamin C levels correlated with basal whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C infusion, percent change in plasma vitamin C level correlated with the percent decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma vitamin C levels seem to play a role in the modulation of insulin action in aged healthy and diabetic subjects.

Aged↗
PubMed1994

Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients.

The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double blind, and cross-over. Each patient was followed up for a prestudy period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P < 0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P < 0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes.

Aged↗
PubMed1994

Insulin resistance and hypertension in the elderly. Optimal drug therapy.

Numerous trials have demonstrated the negative effects of some antihypertensive drugs upon glucose handling. Such findings seem particularly interesting in aged hypertensive patients who are also insulin resistant and affected by physiological changes in the renal and cardiovascular systems. It appears that calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors are the most appropriate drugs to lower blood pressure in aged insulin-resistant hypertensive patients. All calcium channel blockers studied have displayed similar metabolic effects, while among the ACE inhibitors studied, lisinopril was associated with the best metabolic responses. beta-Blockers and thiazide diuretics have strong negative effects on glucose handling. Further studies are needed in order to investigate the metabolic effects of alpha 1-antagonists in aged patients with insulin resistance and hypertension.

Aged↗
PubMed1993

Different contribution of substrates oxidation to insulin resistance in malnourished elderly patients with cancer.

BACKGROUND: The relative contribution of malnutrition and cancer to insulin resistance in elderly patients is still poorly understood. METHODS: Twenty malnourished and 15 well-nourished patients with cancer matched for age (70 +/- 0.3 versus 69 +/- 0.3 years; P = not significant), mean arterial blood pressure (104 +/- 8 versus 107 +/- 7 mm Hg; P = not significant), gender ratio (10 males/10 females versus 7 males/8 females), and sedentary life style underwent an euglycemic glucose clamp. Simultaneous infusion of 3-D-H-glucose and indirect calorimetry allowed the authors to determine glucose turnover parameters and analyze substrates oxidation. RESULTS: Malnourished patients displayed a reduced total body glucose metabolism (36 +/- 2 versus 31 +/- 3 mumol/kg of lean body mass x min P < 0.04) despite higher glucose oxidation. In the same group of patients, the authors demonstrated a significant increase in lipid oxidation and the lack of the inverse relationship between glucose and lipid oxidation (r = 0.07; P = not significant). Insulin infusion enhanced glucose oxidation and suppressed lipid oxidation, but such changes were at lower extent in malnourished patients. CONCLUSIONS: Our study confirms the presence of insulin resistance in malnourished patients and demonstrates the relative contribution of substrates oxidation to the insulin resistance itself.

Aged↗
PubMed1993

Effects of physiological plasma insulin levels on glucose turnover parameters in familial hypercholesterolemia.

Eight young, non-obese patients with primary familial hypercholesterolemia (FH) and 8 healthy subjects matched for age, body mass index, lean body mass, plasma triglyceride and HDL-levels and arterial blood pressure were selected from a lipid clinic. Patients with FH had higher plasma LDL-cholesterol (8.3 +/- 0.5 vs. 4.1 +/- 0.2 mmol/l, P < 0.001) than controls but similar plasma triglyceride (1.15 +/- 0.04 vs. 1.10 +/- 0.02 mmol/l P = NS) levels. Both study groups were submitted to a euglycaemic hyperinsulinemic glucose clamp combined with simultaneous infusion of [3H]glucose to measure insulin action on whole-body glucose uptake and on hepatic glucose production. Two insulin infusion rates (0.15 mU/kg per min from 0 to 120 min and 0.30 mU/kg per min from 121 to 240 min) were used resulting in similar plasma insulin levels in both groups studied. Our results demonstrate that both whole-body glucose uptake and hepatic glucose output are similar in the fasting state as well as during insulin administration in both groups of subjects. We conclude that, in the absence of other causes of insulin resistance, isolated hypercholesterolemia is associated with normal sensitivity to insulin in both liver and peripheral tissues.

Adult↗