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Biomedical subjects

G Paolisso

Publications and source records attributed to G Paolisso.

At least 163 records · Page 9Linked to original sources
PubMed1988

Impaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients.

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p less than 0.001) and patients with diabetes (p less than 0.001). However, even in the presence of 100 mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Plasma glucose lowering effect of sparteine sulphate infusion in non-insulin dependent (type 2) diabetic subjects.

Sparteine sulphate, given i.v. as a bolus of 15 mg/ml plus 90 mg in 0.9% NaCl 100 ml over 60 min, increases plasma insulin and decreases plasma glucose and adrenaline in non-insulin dependent (Type II) diabetic subjects. The hypoglycaemic effect was also evident in the presence of a high plasma glucose level produced by Biostator changing glucose infusion from 20.2 +/- 2.8 to 26.4 +/- 4.2 mg.kg-1.min-1 (p less than 0.01), and it was potentiated by simultaneous infusion of arginine. No additional effect of sparteine on the peripheral sensitivity to insulin were detected by the euglycaemic, hyperinsulinaemic glucose clamp technique, as the glucose infusion rate (3.1 +/- 0.8 vs 2.6 +/- 1.2 mg.kg-1.min-1) was not statistically significant different in the last 60 min of the experiment. It is concluded that sparteine sulphate enhances beta-cell secretion, causing a fall in the plasma glucose concentration.

Adult↗
PubMed1988

Pharmacological doses of oxytocin affect plasma hormone levels modulating glucose homeostasis in normal man.

Pharmacological doses of oxytocin administered in basal conditions evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin and adrenaline levels. The effects of oxytocin on plasma glucagon and adrenaline levels were potentiated by hypoglycemia. When the endogenous pancreas secretion was suppressed by cyclic somatostatin (150 micrograms/h) and exogenous glucagon (3.5 micrograms/h) and insulin (0.2 mU/kg.min) were both replaced, oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels suppressing the glucose infusion rate (GIR) in the first 60 min. On the contrary at higher insulin infusion rate (0.6 mU/kg.min) plasma glucose levels and GIR remained unaffected throughout the study. Oxytocin seems also to potentiate glucose-induced insulin secretion as evidenced by hyperglycemic glucose clamp. In conclusion, pharmacological doses of oxytocin seem to exert a prevalent hyperglycemic effect by a combined action at the liver site (as glycogenolytic agent) and at the endocrine pancreas (as a stimulatory agent of A cell secretion).

Adult↗
PubMed1988

Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes.

The respective modulating effects of continuous and intermittent insulin delivery on pancreatic islet cell function were studied in seven normal men and nine insulin-dependent (type 1) diabetic patients. In the normal men, saline or continuous (0.8 mU kg-1 min-1) or pulsatile (5.2 mU kg-1 min-1, with a switching on/off length of 2/11 min) human insulin were delivered on different days and in random order. Despite hyperinsulinemia, blood glucose was kept close to its basal value by the glucose clamp technique. The diabetic patients also were infused in random order and on different days with either saline or a smaller amount of insulin delivered continuously (0.15 mU kg-1 min-1) or in a pulsatile manner (0.97 mU kg-1 min-1 for 2 min, followed by 11 min during which no insulin was infused). In all experiments, 5 g arginine were given iv as a bolus dose 30 min before the end of the study, and plasma C-peptide and glucagon levels were determined to assess islet cell function. In the normal men, insulin administration resulted in a significant decline of basal plasma glucagon and C-peptide levels and in a clear-cut decrease in the arginine-induced glucagon response. These effects of insulin were significantly more marked when insulin was delivered in a pulsatile rather than a continuous manner. In the insulin-dependent diabetic patients, the lower dose of insulin infused continuously did not alter the basal or arginine-stimulated glucagon response. In contrast, when the same amount of insulin was delivered intermittently, arginine-induced glucagon release was greatly reduced. Thus, these data support the concept that insulin per se is a potent physiological modulator of islet A- and B-cell function. Furthermore, they suggest that these effects of insulin are reinforced when the hormone is administered in an intermittent manner in an attempt to reproduce the pulsatile physiological release of insulin.

Adult↗
PubMed1988

Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients.

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.

Aged↗
PubMed1988

Diabetes and hypertension in the elderly.

Hypertension combined with diabetes in the elderly is characterized by many important metabolic and cardiovascular changes, among which insulin resistance, hyperinsulinaemia and increased total peripheral resistance appear to be the most relevant. Non-insulin dependent diabetes mellitus is also characterized by insulin resistance and hyperinsulinaemia. Moreover, hyperinsulinaemia itself has been shown to increase total peripheral resistance. Hyperinsulinaemia thus seems to play a key role in the pathophysiology of hypertension in elderly diabetic subjects. Therefore elderly hypertensive diabetic patients should be treated with thiazide diuretics in low doses, calcium channel blockers and alpha-adrenergic blockers.

Age Factors↗
PubMed1987

Effect of sparteine sulphate upon basal and nutrient-induced insulin and glucagon secretion in normal man.

Infusion of a therapeutic dose of sparteine sulphate, increased the basal plasma insulin level and lowered plasma glucose. When an intravenous glucose tolerance test was performed with the infusion, the total insulin AUC was significantly larger than in absence of sparteine (2025 vs 1464 microU/ml X min), plasma glucose levels were lower and improved glucose utilization was observed (kg:1.55 vs 1.39%). In the presence of arginine, sparteine sulphate stimulated both beta and alpha cells, increasing both the total insulin (1907 vs 1516 microU/ml X min p less than 0.02) and total glucagon AUCs (7616 +/- 654 vs 6789 +/- 707 pg/ml X min p less than 0.01). Thus, sparteine sulphate increased both basal and nutrient-induced insulin and glucagon secretion in normal man.

Adult↗
PubMed1987

Impaired insulin-mediated erythrocyte magnesium accumulation in essential hypertension.

1. This study was designed to investigate variations in erythrocyte magnesium in the presence of insulin (0.1 unit/l) in hypertensive subjects. 2. Plasma and erythrocyte magnesium levels were found to be significantly lower in hypertensive than in normotensive subjects. 3. The impaired response to insulin (0.1 units/l) of erythrocytes from hypertensive patients was not reversed by elevated extracellular Mg2+ (3.6 mmol/l). 4. Erythrocytes of hypertensive subjects showed an increased membrane microviscosity compared with normotensive subjects. 5. Lidocaine decreased erythrocyte membrane microviscosity and increased erythrocyte magnesium levels in the presence of insulin.

Adult↗
PubMed1987

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man.

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called "evanescent" effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.

Adult↗
PubMed1987

Beta-endorphin infusion restores acute insulin responses to glucose in type-2 diabetes mellitus.

To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated. Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose. An intraislet abnormality of opioid peptides action and/or secretion may play a role in the disturbances of insulin secretion in patients with type-2 diabetes mellitus.

Arginine↗
PubMed1987

Primary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man.

The present study aimed at evaluating the effect of human beta-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h beta-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 +/- 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 +/- 13 ng/l). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of beta-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, beta-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between beta-endorphin and control studies. We conclude that the naturally occurring opioid peptide beta-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of beta-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism.

Adult↗
PubMed1987

The addition of glipizide to insulin therapy in type-II diabetic patients with secondary failure to sulfonylureas is useful only in the presence of a significant residual insulin secretion.

The present study aimed at 1) investigating the effect of a combined insulin + glipizide treatment on the metabolic control (HbA1c levels) and insulin requirements (Biostator assessment) in ten non-obese Type-II diabetic patients with recent secondary failure to sulfonylureas; and 2) characterizing the relative contributions of changes in endogenous insulin secretion (C-peptide response) and insulin sensitivity (insulin-induced glucose disposal in clamped conditions) to this effect. The patients were treated in a randomized cross-over order with either insulin alone or insulin + glipizide (3 X 10 mg/day) during two periods averaging 6 weeks each. Mean HbA1c levels were similar in both experimental conditions (8.2 +/- 0.6 vs 7.9 +/- 0.6%, NS). In fact, during the combined therapy, HbA1c levels decreased in five subjects (from 8.6 +/- 0.7 to 7.1 +/- 0.5%; 'responder'), but not in the five others ('non-responders'); the 20-h Biostator insulin infusion was significantly decreased in the responders (29%; P less than 0.05), but not in the non-responders. Basal (0.271 +/- 0.086 vs 0.086 +/- 0.017 nmol/l; P less than 0.05) and post-glucagon (0.468 +/- 0.121 vs 0.180 +/- 0.060 nmol/l; P less than 0.05) C-peptide plasma levels were significantly higher in the responders than in the non-responders; in addition, glipizide significantly increased basal C-peptide concentrations in the responders only (+68%; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗