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Biomedical subjects

D Giugliano

Publications and source records attributed to D Giugliano.

At least 55 records · Page 3Linked to original sources
PubMed2000

Dietary antioxidants for cardiovascular prevention.

The generation of reactive oxygen species (ROS) is associated with life in aerobic conditions. ROS are thought to be implicated in the pathogenesis of various human diseases since they are capable of damaging biological macromolecules such as DNA, carbohydrates and proteins. The organism maintains defense against ROS, including enzymes and low molecular-weight antioxidants. An important source of antioxidants is diet which contains numerous compounds exhibiting antioxidant activity. A shortage of antioxidants in the diet might promote coronary heart disease through accumulation of oxidized LDL in macrophages. However, antioxidants may also influence endothelial functions, smooth muscle cell proliferation, thrombosis and plaque rupture. Consumption of fruits and vegetables, olive oil, red wine and tea is inversely correlated with heart disease rates. These foods are particularly rich in natural antioxidant nutrients, including ascorbate (vitamin C), the tocopherols (vitamin E) and carotenoids. More than 600 naturally occurring carotenoids have been identified. These compounds are plant pigments that provide the bright color of various fruits and vegetables; lycopene, which gives tomatoes their red color, is under active research. Flavonoids are > 4,000 naturally occurring substances which provide color, texture and taste for plant foods. As free radical scavengers, flavonoids inhibit lipid peroxidation, promote vascular relaxation and help prevent atherosclerosis. A sufficient supply with antioxidants from diet might help prevent or delay the occurrence of pathological changes associated with oxidative stress. When diet fails to meet the antioxidant requirement, dietary supplements might be indicated. The recently coined term nutriceuticals describes a variety of nonprescription products that are used to enhance health. The best known are vitamin E, vitamin C, carotenoids, coenzyme Q10, flavonoids and the amino acid L-arginine. Rigorous clinical trials, particularly among high-risk groups, are needed before they can be recommended routinely to patients.

Antioxidants↗
PubMed1999

Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins.

CONTEXT: Increased levels of homocysteine are associated with risk of cardiovascular disease. Homocysteine may cause this risk by impairing endothelial cell function. OBJECTIVE: To evaluate the effect of acute hyperhomocysteinemia with and without antioxidant vitamin pretreatment on cardiovascular risk factors and endothelial functions. DESIGN AND SETTING: Observer-blinded, randomized crossover study conducted at a university hospital in Italy. SUBJECTS: Twenty healthy hospital staff volunteers (10 men, 10 women) aged 25 to 45 years. INTERVENTIONS: Subjects were given each of 3 loads in random order at 1-week intervals: oral methionine, 100 mg/kg in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). Ten of the 20 subjects also ingested a placebo load with vitamins. MAIN OUTCOME MEASURES: Lipid, coagulation, glucose, and circulating adhesion molecule parameters, blood pressure, and endothelial functions as assessed by hemodynamic and rheologic responses to L-arginine, evaluated at baseline and 4 hours following ingestion of the loads. RESULTS: The oral methionine load increased mean (SD) plasma homocysteine level from 10.5 (3.8) micromol/L at baseline to 27.1 (6.7) micromol/L at 4 hours (P<.001). A similar increase was observed with the same load plus vitamins (10.0 [4.0] to 22.7 [7.8] micromol/L; P<.001) but no significant increase was observed with placebo (10.1 [3.7] to 10.4 [3.2] micromol/L; P=.75). Coagulation and circulating adhesion molecule levels significantly increased after methionine ingestion alone (P<.05) but not after placebo or methionine ingestion with vitamins. While the mean (SD) blood pressure (-7.0% [2.7%]; P<.001), platelet aggregation response to adenosine diphosphate (-11.4% [4.5%]; P=.009) and blood viscosity (-3.0% [1.2%]; P=.04) declined in these parameters 10 minutes after an L-arginine load (3 g) following placebo, the increase after methionine alone (-2.3% [1.5%], 4.0% [3.0%], and 1.5% [1.0%], respectively; P<.05), did not occur following methionine load with vitamin pretreatment (-6.3% [2.5%], -7.9% [3.5%], and -1.5% [1.0%], respectively; P=.24). CONCLUSION: Our data suggest that mild to moderate elevations of plasma homocysteine levels in healthy subjects activate coagulation, modify the adhesive properties of endothelium, and impair the vascular responses to L-arginine. Pretreatment with antioxidant vitamin E and ascorbic acid blocks the effects of hyperhomocysteinemia, suggesting an oxidative mechanism.

Acute Disease↗
PubMed1999

Advancing age and insulin resistance: new facts about an ancient history.

The relationship between advancing age and insulin resistance is widely known, but the cause(s) of such association are less well understood. Age-related changes in anthropometric characteristics and environmental factors (changes in diet habits and decline in physical activity) have been hypothesized as being among the main causes. More recently, the role of plasma insulin-like growth factor I (IGF-I), dehydroepiandrosterone sulphate (DHEAS) and tumour necrosis factor alpha (TNF-alpha) concentrations as well as the degree of oxidative stress have also been evaluated. As far as the anthropometric changes are concerned, a decline in fat-free mass and a relative or absolute increase in fat mass are common findings in aged subjects. Such changes are combined with a decline in plasma DHEAS and IGF-I concentration and a rise in plasma TNF-alpha concentrations and oxidative stress, which, in turn, may interact with the anthropometric changes determining the worsening in insulin-mediated glucose uptake. Finally, age-related environmental factors (changes in diet quality and decline in the degree of physical activity) might be a common factor allowing anthropometric factors and age-related remodelling to accelerate their negative impact on insulin action.

Aging↗
PubMed1999

Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.

OBJECTIVE: Healthy centenarians have a greater molar ratio of plasma insulin-like growth factor-1 to insulin-like growth factor binding protein-3 than that of aged subjects. We investigated the question of whether differences in mean arterial pressure and in this plasma ratio were related in healthy centenarians. SUBJECTS AND METHODS: We studied 52 subjects in total, 30 aged subjects (70-99 years) and 22 healthy centenarians (> 100 years) to determine differences in mean arterial pressure, endothelial function and intracellular cation levels. RESULTS: In the healthy centenarians, the molar ratio of fasting plasma insulin-like growth factor-1 to its binding protein-3 was significantly correlated with mean arterial pressure (r = -0.66, P < 0.001). Baseline (19.3 +/- 1.5 versus 27.6 +/- 2.2 mumol/l, P < 0.05) and L-arginine-stimulated percentage increases in the plasma total nitrate: nitrite ratio (67 +/- 3.4 versus 48 +/- 4.5%, P < 0.03) were greater in the healthy centenarians than in the aged subjects. An L-arginine bolus elicited an increase in forearm blood flow which was correlated with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.79, P < 0.001) and with the fasting erythrocyte magnesium concentration (r = 0.80, P < 0.001) in healthy centenarians. Both correlations remained significant (P < 0.01) after adjustment for sex, body mass index and the waist: hip ratio. Moreover, the fasting plasma molar ratio of insulin-like growth factor-1 to its binding protein-3 was correlated with the percentage increase in forearm blood flow (r = 0.59, P < 0.005) and with the percentage increase in the plasma total nitrate: nitrite ratio (r = 0.54, P < 0.009) in healthy centenarians. The centenarians had higher baseline total erythrocyte magnesium and lower calcium concentrations than the aged subjects. The addition of insulin growth factor-1 to the incubation medium increased the total intracellular erythrocyte magnesium content and decreased the calcium content in both groups of subjects. Nevertheless, the percentage increase in total erythrocyte magnesium (33 +/- 3.8 versus 12 +/- 3.4%, P < 0.03) and decline in intracellular calcium (17 +/- 2.8 versus 8 +/- 3.1%, P < 0.02) concentrations were greater in the healthy centenarians than the aged subjects. CONCLUSION: In healthy centenarians, insulin-like growth factor-1 may preserve endothelial function and modulate the intracellular cation content, thus contributing to a lower mean arterial pressure than that in aged subjects.

Aged↗
PubMed1998

Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes.

Studies have shown that a high plasma non-esterified fatty acid concentration may inhibit glucose induced insulin secretion in vitro and in vivo. The effect of lowering the fatty acid concentration on the acute insulin response was investigated in first degree relatives of people with Type II diabetes in a double-blind, randomised, placebo-controlled trial. Fifty first degree relatives of people with Type II diabetes volunteered for the study. Twenty five were given acipimox (250 mg/day, four times daily) and 25 placebo. The group treated with acipimox had a lower 2-h plasma glucose concentration (6.1 +/- 0.2 vs 7.7 +/- 0.3 vs mmol/l, p < 0.01); better insulin-mediated glucose uptake (35.4 +/- 0.5 vs 28.3 +/- 0.4 mumol/kg fat free mass per min, p < 0.01), acute insulin response (68 +/- 4.4 vs 46 +/- 7.3 mU/l, p < 0.01) and respiratory quotient (0.81 +/- 0.02 vs 0.77 +/- 0.03, p < 0.05); and a rise in the plasma glucagon (164 +/- 63 vs 134 +/- 72 ng/1, p < 0.05), growth hormone (1.31 +/- 0.13 vs 0.97 +/- 0.21 microgram/l, p < 0.03) and cortisol (325 +/- 41 vs 284 +/- 139 nmol/l, p < 0.05) concentrations. The difference in the acute insulin response persisted, even after adjustment for the 2-h plasma glucose concentration, insulin-mediated glucose uptake, the fasting plasma glucagon concentration and the growth hormone concentration (p < 0.05). In a subgroup of eight patients acipimox was compared with acipimox plus intralipid. The acute insulin response (44 +/- 5.1 vs 71 +/- 5.3 mU/l, p < 0.01) and the insulin-mediated glucose uptake (27.4 +/- 0.4 vs 36.7 +/- 0.5 mumol/kg fat free mass per min, p < 0.003) were lower with acipimox plus intralipid treatment than with acipimox alone. It is concluded that long term acipimox treatment lowers the plasma fasting free fatty acid concentration and improves the acute insulin response and the insulin mediated glucose uptake.

Adult↗
PubMed1998

Hemodynamic and metabolic effects of transdermal clonidine in patients with hypertension and non-insulin-dependent diabetes mellitus.

The aim of this study was to evaluate the effect of transdermal clonidine on hemodynamic and metabolic parameters in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in placebo period, 20 NIDDM patients who had diastolic blood pressure in the range of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled, cross-over study of 4 week treatment with clonidine (transdermal patch 2.5 mg/week) or placebo (inactive patch). Compared with placebo, clonidine significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v 98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99 +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P < .01). Oxidative glucose disposal (indirect calorimetry) was also greater after clonidine. Plasma glucose, insulin, and C-peptide responses following oral glucose (75 g) were significantly lower after clonidine, as well as urinary albumin excretion. Transdermal clonidine is effective in reducing blood pressure in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce the cardiovascular impact of hypertension in diabetes mellitus.

Administration, Cutaneous↗
PubMed1998

Effect of metformin on food intake in obese subjects.

BACKGROUND: It has been hypothesized that metformin inhibits food intake, but in humans such effect needs to be demonstrated. Our study aims at investigating the effect of metformin administration on food intake in obese, non-diabetic, normotensive patients. METHODS: Thirty patients underwent a double-blind, randomized study. Placebo (P; n = 15) and metformin (M; n = 15) were both given for 15 days, and food intake (FI) was recorded at baseline and in the last 4 days of each treatment period. RESULTS: M administration allowed a stronger decline in body weight (BW) (-2.8 +/- 1.6 vs. -0.3 +/- 0.4 kg P < 0.01), body fat (BF) (-1.4 +/- 1.2 vs. -0.3 +/- 1.1 kg P < 0.01), plasma leptin concentration (-5.2 +/- 8.9 vs. -1.8 +/- 10.4 ng mL-1 P < 0.05) and FI (-642 +/- 491 vs.-70 +/- 1165 kJ per 24 h P < 0.01) than P. In M-treated subjects, changes in FI significantly correlated with those in BW (r = 0.63, P < 0.007) and BF (r = 0.74, P < 0.001). Independently of sex and change in BF, the changes in FI and in fasting plasma leptin concentration (r = 0.58, P < 0.01) were still correlated. CONCLUSION: Our study suggests that metformin administration is useful to inhibit FI and to lower BW and BF in obese non-diabetic patients.

Adolescent↗
PubMed1998

Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha.

In 70 healthy subjects with a large age range, the relationships between plasma tumor necrosis factor-alpha (TNF-alpha) and body composition, insulin action, and substrate oxidation were investigated. In the cross-sectional study (n = 70), advancing age correlated with plasma TNF-alpha concentration (r = 0.64, P < 0.001) and whole body glucose disposal (WBGD; r= -0.38, P < 0.01). The correlation between plasma TNF-alpha and age was independent of sex and body fat (BF; r = 0.31, P < 0.01). Independent of age and sex, a significant relationship between plasma TNF-alpha and leptin concentration (r = 0.29, P < 0.02) was also found. After control for age, sex, BF, and waist-to-hip ratio (WHR), plasma TNF-alpha was still correlated with WBGD (r = -0.33, P < 0.007). Further correction for plasma free fatty acid (FFA) concentration made the latter correlation no more significant. In a multivariate analysis, a model made by age, sex, BF, fat- free mass, WHR, and plasma TNF-alpha concentrations explained 69% of WBGD variability with age (P < 0.009), BF (P < 0.006), fat-free mass (P < 0.005), and plasma TNF-alpha (P < 0.05) significantly and independently associated with WBGD. In the longitudinal study, made with subjects at the highest tertiles of plasma TNF-alpha concentration (n = 50), plasma TNF-alpha concentration predicted a decline in WBGD independent of age, sex, BF, WHR [relative risk (RR) = 2.0; 95% confidence intervals (CI) = 1.2-2.4]. After further adjustment for plasma fasting FFA concentration, the predictive role of fasting plasma TNF-alpha concentration on WBGD (RR = 1.2; CI = 0.8-1.5) was no more significant. In conclusion, our study demonstrates that plasma TNF-alpha concentration is significantly associated with advancing age and that it predicts the impairment in insulin action with advancing age.

Adult↗
PubMed1998

Effects of perindopril and carvedilol on endothelium-dependent vascular functions in patients with diabetes and hypertension.

OBJECTIVE: To compare the effects of the ACE inhibitor perindopril and the beta-blocker carvedilol on blood pressure and endothelial functions in NIDDM patients with hypertension. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4-8 mg daily) or carvedilol (25-50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide. RESULTS: Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05-0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group. CONCLUSIONS: At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.

Adrenergic beta-Antagonists↗
PubMed1997

Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension. A randomized, controlled trial.

BACKGROUND: Diabetic patients are considered less suitable than nondiabetic patients for beta-blocker therapy because of the risk for worsened glucose and lipid metabolism and more severe hypoglycemic attacks. OBJECTIVE: To compare the metabolic and cardiovascular effects of carvedilol with those of atenolol in diabetic patients with hypertension. DESIGN: Randomized, double-blind, 24-week trial. SETTING: University hospital clinic. PATIENTS: 45 patients with non-insulin-dependent diabetes mellitus and hypertension. INTERVENTION: After a 4- to 6-week run-in period during which placebo was given in a single-blind manner, patients were randomly assigned to carvedilol or atenolol. MEASUREMENTS: An oral glucose tolerance test; assessment of insulin sensitivity and hormonal responses to insulin hypoglycemia; and assessment of lipid levels, blood pressure, left ventricular mass, and lipid peroxidation. RESULTS: Changes in systolic and diastolic blood pressure and left ventricular mass index were similar with carvedilol and atenolol (P > 0.2). Fasting plasma glucose and insulin levels decreased with carvedilol and increased with atenolol. Responses to carvedilol were greater than those to atenolol, as follows: increase in total glucose disposal, 9.54 mumol/kg of body weight per minute (95% CI, 7 to 11.9 mumol/kg per minute); decrease in plasma glucose response to oral glucose, 61 mmol/L x 180 minutes (CI, -101 to -21 mmol/L x 180 minutes); decrease in insulin response to oral glucose, 6.2 nmol/L x 180 minutes (CI, -9.8 to -2.6 nmol/L x 180 minutes); decrease in triglyceride level, 0.56 mmol/L (CI, -0.75 to -0.37 mmol/L; P < 0.001); increase in high-density lipoprotein cholesterol level, 0.13 mmol/L (CI, 0.09 to 0.17 mmol/L; P < 0.001); and decrease in lipid peroxidation, 0.25 mumol/L (CI, -0.34 to -0.16 mumol/L). CONCLUSIONS: By improving glucose and lipid metabolism and reducing lipid peroxidation, carvedilol may offer advantages in patients with diabetes and hypertension.

Adrenergic alpha-Antagonists↗
PubMed1997

Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia.

BACKGROUND: Acute hyperglycemia may increase vascular tone in normal humans via a glutathione-sensitive, presumably free radical-mediated pathway. The objective of this study was to investigate whether or not the vascular effects of hyperglycemia are related to reduced availability of nitric oxide. METHODS AND RESULTS: Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial pancreas. Systolic and diastolic blood pressures, heart rate, and plasma catecholamines showed significant increases (P < .05) starting after 30 minutes of hyperglycemia; leg blood flow decreased significantly (15%; P < .05) at 60 and 90 minutes. Platelet aggregation to ADP and blood viscosity also showed significant increments (P < .05). The infusion of L-arginine (n = 7, 1 g/min) but not D-arginine (n = 5, 1 g/min) or L-lysine (n = 5, 1 g/min) in the last 30 minutes of the hyperglycemic clamp completely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of NG-monomethyl-L-arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis in 8 normal subjects produced vascular effects qualitatively similar to those of hyperglycemia but quantitatively higher (P < .05); however, heart rate and plasma catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyperglycemia produced changes not different from those obtained during infusion of L-NMMA alone. CONCLUSIONS: The results show that acute hyperglycemia in normal subjects causes significant hemodynamic and rheological changes that are reversed by L-arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but not entirely, by infusion of L-NMMA. This suggests that hyperglycemia may reduce nitric oxide availability in humans.

Acute Disease↗
PubMed1997

The vascular effects of L-Arginine in humans. The role of endogenous insulin.

This study aimed at evaluating whether increased availability of the natural precursor of nitric oxide, L-arginine, could influence systemic hemodynamic and rheologic parameters in humans and whether the effects of L-arginine are mediated by endogenous insulin. 10 healthy young subjects participated in the following studies: study I, infusion of L-arginine (1 g/min for 30 min); study II, infusion of L-arginine plus octreotide (25 microg as i.v. bolus + 0.5 microg/min) to block endogenous insulin and glucagon secretion, plus replacement of basal insulin and glucagon; study III, infusion of L-arginine plus octreotide plus basal glucagon plus an insulin infusion designed to mimic the insulin response of study I. L-Arginine infusion significantly reduced systolic (11+/-3, mean+/-SE) and diastolic (8+/-2 mmHg, P < 0.001) blood pressure, platelet aggregation (20+/-4%), and blood viscosity (1.6+/-0.2 centipois, P < 0.01), and increased leg blood flow (97+/-16 ml/min), heart rate, and plasma catecholamine levels (P < 0.01). In study II, plasma insulin levels remained suppressed at baseline; in this condition, the vascular responses to L-arginine were significantly reduced, except for plasma catecholamines which did not change significantly. In study III, the plasma insulin response to L-arginine was reestablished; this was associated with hemodynamic and rheologic changes following L-arginine not significantly different from those recorded in study I. These findings show that systemic infusion of L-arginine in healthy subjects induces vasodilation and inhibits platelet aggregation and blood viscosity. These effects are mediated, in part, by endogenous released insulin.

Adult↗
PubMed1997

Effect of insulin on blood rheology in non-diabetic subjects and in patients with Type 2 diabetes mellitus.

We evaluated the effect of insulin on platelet function, blood viscosity, and filterability in healthy subjects and in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Fifteen diabetic patients were free from cardiovascular complications (group A), while the other 15 patients had both clinical and measured evidence of coronary or peripheral vascular disease (group B); 15 non-diabetic subjects served as controls. On blood samples taken without stasis, maximal platelet aggregation to 1.25 micromol l(-1) ADP, blood and plasma viscosity, and blood filterability were measured in basal conditions, and after incubation of blood, plasma or platelet-rich plasma with insulin at two physiological concentrations (120 and 480 pmol l(-1)). Compared with healthy subjects, the diabetic patients of group B had higher values of blood (p < 0.01) and plasma (p < 0.05) viscosity, and platelet aggregation response to ADP (p < 0.01), as well as lower values of blood filterability (p < 0.01). The diabetic patients of group A had values intermediate between normal subjects and the patients of group B. In non-diabetic subjects, insulin significantly decreased platelet aggregation and blood viscosity at low shear rates (22.5 s(-1)) (p < 0.01 for both), and had no significant effects on other parameters. In the diabetic patients of group A, insulin decreased blood viscosity at high (225 s(-1)) rates of shear (p < 0.01) and increased blood filterability (p < 0.01). The effects of insulin were not dose-related. In the diabetic patients of group B, none of the parameters evaluated was significantly influenced by insulin. Type 2 diabetic patients present many abnormalities of the rheologic properties of blood. The beneficial effects of insulin on platelet aggregation and blood viscosity are not evident in Type 2 diabetic patients, especially those with vascular complications and this may be relevant to the development of those complications.

Adenosine Diphosphate↗
PubMed1997

L-arginine but not D-arginine stimulates insulin-mediated glucose uptake.

Our study aims at investigating a possible role for L-arginine and D-arginine in insulin-mediated glucose uptake. Twelve lean healthy subjects volunteered for the study and were submitted to three euglycemic-hyperinsulinemic glucose clamps to investigate the effect of L-arginine (0.5 g/min in the last 60 minutes of the clamp), D-arginine (0.5 g/min in the last 60 minutes of the clamp), and saline 0.9% NaCl on insulin-mediated glucose uptake. All tests were made in random order. In study 1, L-arginine versus saline infusion was associated with a significant increase in blood flow (131% +/- 7% v 87% +/- 5%, P < .001) and whole-body glucose disposal ([WBGD] 61.4 +/- 4.4 v 41.3 +/- 3.5 mumol/kg fat-free mss [FFM].min, P < .001). Analysis of substrate oxidation demonstrated that both oxidative and nonoxidative glucose metabolism was improved by L-arginine delivery. After adjustment for the change in blood flow, WBGD was still greater after L-arginine than after saline infusion. Along with L-arginine infusion and independently of the change in blood flow, the percent change in WBGD correlated with the percent change in plasma cGMP (r = .55, P < .05). D-Arginine infusion did not affect insulin-mediated glucose uptake. In particular, WBGD (42.1 +/- 3.4 v 41.3 +/- 3.5 mumol/kg FFM.min, P = NS) was similar in both experimental conditions. Basal levels (2.8 +/- 0.2 v 2.7 +/- 0.3 nmol/L, P = NS) and the insulin-mediated increase (43% +/- 5% v 39% +/- 4%, P = NS) in plasma cGMP were also superimposable along with insulin plus D-arginine and insulin alone, respectively. Finally, blood flow (224 +/- 29 v 230 +/- 35 mL/min, P = NS) was not different at baseline and was similarly stimulated (84% +/- 4% v 87% +/- 5%, P = NS) by insulin infusion. In conclusion, L-arginine but not D-arginine stimulates insulin-mediated glucose uptake. Nitric oxide (NO), the metabolic mediator for L-arginine, potentiates insulin-mediated glucose uptake through the increase in blood flow. Nevertheless, an independent effect of intracellular cGMP on WBGD cannot be ruled out.

Adult↗
PubMed1997

L-arginine for testing endothelium-dependent vascular functions in health and disease.

The objective of this study was to assess the role of L-arginine, the natural precursor of nitric oxide, for testing endothelial function in physiological and pathophysiological conditions. In an initial study of 20 healthy subjects, mean blood pressure decreases in response to increasing doses of L-arginine (1, 2, 3, and 5 g) were 1.1 +/- 1.3, 2.6 +/- 1.5, 7.6 +/- 1.3, and 7.7 +/- 2 mmHg, respectively, P < 0.01. The enantiomer D-arginine (3 g) did not produce any change in mean blood pressure and platelet aggregation (n = 10), whereas the infusion of the L-arginine analog NG-monomethyl-L-arginine (6 mg/min) reduced by 70% the vascular effects of L-arginine. In the whole population of 52 healthy subjects, there was an inverse correlation between age and blood pressure or platelet aggregation changes after L-arginine. Compared with matched controls (n = 20), the changes in mean blood pressure and platelet aggregation after L-arginine were significantly lower in non-insulin-dependent diabetic (n = 20) and hypercholesterolemic (n = 16), but not in hypertensive (n = 20), subjects. Changes in blood viscosity were significantly lower only in hypercholesterolemic subjects. Our findings suggest that an intravenous bolus of 3 g L-arginine may be a simple and useful tool to assess the endothelial control of blood pressure and platelet activity in health and disease.

Adenosine Diphosphate↗