References of "Paolisso, G"
     in
Bookmark and Share    
Peer Reviewed
See detailLe vieillissement s'accompagne-t-il d'une diminution de la sensibilite a l'insuline? Roles de l'IGF1 et de la dehydroepiandrosterone.
Paolisso, G.; Tagliamonte, M. R.; Rizzo, M. R. et al

in Journées Annuelles de Diabetologie de l'Hôtel-Dieu (1999)

Detailed reference viewed: 7 (0 ULg)
Peer Reviewed
See detailExhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.
Castillo, M. J.; Scheen, André ULg; Paolisso, G. et al

in Annales d'Endocrinologie (1996), 57(5), 395-402

AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients ... [more ▼]

AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3, 5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients tested at near-baseline blood glucose levels, the blood glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels. [less ▲]

Detailed reference viewed: 12 (0 ULg)
Peer Reviewed
See detailGlucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.
Scheen, André ULg; Paquot, Nicolas ULg; Letiexhe, Michel ULg et al

in International Journal of Obesity & Related Metabolic Disorders (1995), 19 Suppl 3

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 38 (2 ULg)
Peer Reviewed
See detailGlucose handling, diabetes and ageing.
Paolisso, G.; Scheen, André ULg; Lefebvre, Pierre ULg

in Hormone Research (1995), 43(1-3), 52-7

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 15 (1 ULg)
Peer Reviewed
See detailChanges in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients.
Paolisso, G.; Scheen, André ULg; Cozzolino, D. et al

in Journal of Clinical Endocrinology and Metabolism (1994), 78(6), 1510-4

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 10 (0 ULg)
Peer Reviewed
See detailMagnesium et metabolisme glucidique.
Lefebvre, Pierre ULg; Paolisso, G.; Scheen, André ULg

in Thérapie (1994), 49(1), 1-7

The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in ... [more ▼]

The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insufficient magnesium intakes and increase magnesium losses, particularly in the urine. In type 2, or non-insulin-dependent, diabetes mellitus, magnesium deficiency seems to be associated with insulin resistance. Furthermore, it may participate in the pathogenesis of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion of diabetic women, in fetal malformations and in the pathogenesis of neonatal hypocalcemia of the infants of diabetic mothers. Administration of magnesium salts to patients with type 2 diabetes tend to reduce insulin resistance. Long-term studies are needed before recommending systematic magnesium supplementation to type 2 diabetic patients with subclinical magnesium deficiency. [less ▲]

Detailed reference viewed: 110 (1 ULg)
Peer Reviewed
See detailInsulin secretion and action in various populations with type 2 (non-insulin-dependant) diabetes mellitus
Scheen, André ULg; Paolisso, G.; Castillo, M. et al

in Diabetologia (1992), 16 ( suppl 1)(29), 116

Detailed reference viewed: 10 (0 ULg)
Peer Reviewed
See detailInsulin effects on glucose kinetics in non-insulin-dependent diabetic patients with secondary failure to hypoglycaemic agents: role of different modes and rates of delivery.
Paolisso, G.; Sgambato, S.; Varricchio, M. et al

in European Journal of Medicine (The) (1992), 1(5), 261-7

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 7 (0 ULg)
Peer Reviewed
See detailPulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency.
Paolisso, G.; Scheen, André ULg; Giugliano, D. et al

in Journal of Clinical Endocrinology and Metabolism (1991), 72(3), 607-15

The aim of this study was to see if the greater effect of insulin on hepatic glucose output when insulin is given using 13-min pulses in man remains when the same amount of insulin is delivered using 26 ... [more ▼]

The aim of this study was to see if the greater effect of insulin on hepatic glucose output when insulin is given using 13-min pulses in man remains when the same amount of insulin is delivered using 26-min pulses. The study was performed on nine male healthy volunteers submitted to a 325 min glucose-controlled glucose iv infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin. Three experiments were performed in each subject on different days and in random order. In all cases glucagon was replaced (58 ng min-1). The amounts of insulin infused were identical in all instances and were 0.2 mU kg-1 min-1 (continuous), 1.3 mU kg-1 min-1, 2 min on and 11 min off (13-min pulses) or 2.6 mU kg-1 min-1, 2 min on and 24 min off (26-min pulses). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using D-[3-3H] glucose infusion allowed to study glucose turnover. When compared with continuous insulin, 13-min insulin pulses induced a significantly greater inhibition of endogenous glucose production. This effect disappeared when insulin was delivered in 26-min pulses. We conclude that, in man, an adequate pulse frequency is required to allow the appearance of the greater inhibition of pulsatile insulin on endogenous glucose production. [less ▲]

Detailed reference viewed: 12 (0 ULg)
Peer Reviewed
See detailImprovement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine.
Scheen, André ULg; Paolisso, G.; Salvatore, T. et al

in Diabetes Care (1991), 14(4), 325-32

OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo ... [more ▼]

OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo-controlled crossover trial with 1-wk treatment periods (2 x 15 mg/day d-fenfluramine) was conducted. Twenty obese subjects, 10 with normal oral glucose tolerance and 10 with non-insulin-dependent diabetes mellitus (NIDDM), were all treated with a weight-maintaining diet. Euglycemic-hyperinsulinemic glucose clamps with measurement of glucose kinetics with D-[3-3H]glucose were performed at either two (patients without NIDDM, 0.05 and 0.10 U.kg-1.h-1) or three (patients with NIDDM, 0.05, 0.10, and 0.50 U.kg-1.h-1) insulin delivery rates. RESULTS: In the nondiabetic subjects, no significant changes in any metabolic or hormonal parameter were measured in the basal state or during the clamp despite a slight reduction in body weight (-1.2 +/- 0.5 kg, P less than 0.05). In the diabetic patients, no significant changes in body weight or basal plasma insulin levels were observed, but fasting blood glucose levels (8.0 +/- 0.8 vs. 9.4 +/- 1.1 mM, P less than 0.005) and plasma free fatty acid concentrations (1150 +/- 227 vs. 1640 +/- 184 microM, P less than 0.05) were significantly reduced after d-fenfluramine compared with placebo. During the clamp, insulin metabolic clearance rate (MCR) was similar after both placebo and d-fenfluramine; endogenous (hepatic) glucose production was similarly and almost completely suppressed, whereas glucose disposal was remarkably enhanced after d-fenfluramine (average increase of glucose MCR 35 +/- 12%, P less than 0.02). CONCLUSIONS: Whatever the mechanism(s) involved, a 1-wk treatment with d-fenfluramine induces better blood glucose control and improves insulin sensitivity in obese patients with NIDDM independent of significant weight reduction; this last effect is not present in obese subjects with normal oral glucose tolerance. [less ▲]

Detailed reference viewed: 8 (1 ULg)
Peer Reviewed
See detailPulsatile glucagon has greater hyperglycaemic, lipolytic and ketogenic effects than continuous hormone delivery in man: effect of age.
Paolisso, G.; Buonocore, S.; Gentile, S. et al

in Diabetologia (1990), 33(5), 272-7

The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight ... [more ▼]

The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2 +/- 1.2 years) and in eight healthy aged subjects (69.4 +/- 2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non-esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma beta-hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and beta-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced. [less ▲]

Detailed reference viewed: 14 (0 ULg)
Peer Reviewed
See detailMagnesium and glucose homeostasis.
Paolisso, G.; Scheen, André ULg; D'Onofrio, F. et al

in Diabetologia (1990), 33(9), 511-4

Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been ... [more ▼]

Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been recently studied. In particular it has been shown that magnesium plays the role of a second messenger for insulin action; on the other hand, insulin itself has been demonstrated to be an important regulatory factor of intracellular magnesium accumulation. Conditions associated with insulin resistance, such as hypertension or aging, are also associated with low intracellular magnesium contents. In diabetes mellitus, it is suggested that low intracellular magnesium levels result from both increased urinary losses and insulin resistance. The extent to which such a low intracellular magnesium content contributes to the development of macro- and microangiopathy remains to be established. A reduced intracellular magnesium content might contribute to the impaired insulin response and action which occurs in Type 2 (non-insulin-dependent) diabetes mellitus. Chronic magnesium supplementation can contribute to an improvement in both islet Beta-cell response and insulin action in non-insulin-dependent diabetic subjects. [less ▲]

Detailed reference viewed: 36 (0 ULg)
Peer Reviewed
See detailEffects of pulsatile delivery of insulin and glucagon in humans.
Paolisso, G.; Scheen, André ULg; Albert, Adelin ULg et al

in American Journal of Physiology (1989), 257(5 Pt 1), 686-96

The purpose of the present study was to investigate the respective effects of continuous intravenous delivery of both insulin and glucagon compared with those of pulsatile insulin (and continuous glucagon ... [more ▼]

The purpose of the present study was to investigate the respective effects of continuous intravenous delivery of both insulin and glucagon compared with those of pulsatile insulin (and continuous glucagon), pulsatile glucagon (and continuous insulin) and both hormones administered in a pulsatile manner (but out of phase) on various parameters of glucose turnover. The study was performed on six healthy male volunteers submitted to a 325-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin (2 micrograms/min). Four combinations of continuous and pulsatile infusions of insulin and glucagon were performed on different days and in random order. The amounts of hormone infused were identical in all instances and were 0.2 mU.kg-1.min-1 (continuous insulin), 67 ng/min (continuous glucagon), 1.3 mU.kg-1.min-1 and 435 ng/min with a switching on-off length of 2-11 min (for intermittent insulin and glucagon delivery, respectively). In the case of pulsatile administration of both hormones, the pulses of insulin and glucagon were given out of phase with a 6-min interval. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using a D-[3-3H]glucose infusion allowed to study glucose turnover. When compared with pulsatile insulin and continuous glucagon, pulsatile glucagon and continuous insulin were characterized by a significantly higher endogenous (hepatic) glucose production. When both insulin and glucagon were delivered in a pulsatile manner, the effect of pulsatile glucagon was predominant, maintaining a high endogenous glucose production. Under no circumstance was an effect on glucose utilization or clearance detected. This study demonstrates that pulsatile delivery of insulin or glucagon in humans has greater effects in modulating endogenous glucose production than continuous infusion. Furthermore, when both insulin and glucagon are delivered intermittently and out of phase, the stimulatory effect of glucagon on endogenous glucose production prevails over the inhibitory effect of insulin. [less ▲]

Detailed reference viewed: 23 (0 ULg)
Peer Reviewed
See detailPulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes.
Paolisso, G.; Sgambato, S.; Torella, R. et al

in Journal of Clinical Endocrinology and Metabolism (1988), 66(6), 1220-6

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 8 (1 ULg)
Peer Reviewed
See detailImpaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients.
Paolisso, G.; Sgambato, S.; Giugliano, D. et al

in Diabetologia (1988), 31(12), 910-5

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 ... [more ▼]

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) [less ▲]

Detailed reference viewed: 14 (0 ULg)
Peer Reviewed
See detailGreater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels.
Paolisso, G.; Sgambato, S.; Passariello, N. et al

in Diabetes (1987), 36(5), 566-70

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic ... [more ▼]

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady-state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels. [less ▲]

Detailed reference viewed: 7 (0 ULg)
Peer Reviewed
See detailPrevention of metabolic alterations by insulin supplements administered either before or after 2-h nocturnal interruption of CSII.
Scheen, André ULg; Henrivaux, P.; Jandrain, Bernard ULg et al

in Diabetes Care (1987), 10(5), 567-72

To evaluate the efficacy of a bolus insulin injection to prevent the metabolic alterations induced by a 2-h nocturnal interruption of a continuous subcutaneous insulin infusion (CSII), nine type I ... [more ▼]

To evaluate the efficacy of a bolus insulin injection to prevent the metabolic alterations induced by a 2-h nocturnal interruption of a continuous subcutaneous insulin infusion (CSII), nine type I (insulin-dependent) C-peptide-negative diabetic patients were studied from 2200 to 0800 h during two randomized tests. An insulin bolus (2.1 +/- 0.2 U) was administered via the pump either at 2300 h, just before CSII interruption, or at 0100 h, after reactivating the pump at its usual basal rate (1.05 +/- 0.11 U/h). The insulin bolus at 2300 h induced a significant rise in plasma free-insulin levels at 2400 h (+6.9 +/- 1.8 mU/L, P less than .01), resulting in an early and marked fall in blood glucose concentrations between 2300 and 0100 h (-2.7 +/- 0.5 mM, P less than .001), with hypoglycemic values in five patients. The insulin bolus at 0100 h counteracted the fall in plasma free-insulin levels observed between 2300 and 0100 h and significantly increased plasma insulin at 0200 h (+3.2 +/- 0.8 mU/L, P less than .01). Blood glucose concentrations that remained stable during the 2-h arrest of the pump fell significantly between 0100 and 0400 h (-2.1 +/- 0.5 mM, P less than .005). This fall rate was significantly lower than that measured within the 3 h after the insulin bolus given before CSII interruption but significantly higher than that observed in a reference control group of patients whose pump was functioning normally throughout the night.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Detailed reference viewed: 8 (0 ULg)
Peer Reviewed
See detailPulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man.
Paolisso, G.; Scheen, André ULg; Luyckx, A. S. et al

in American Journal of Physiology (1987), 252(1 Pt 1), 1-7

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 13 (0 ULg)
Peer Reviewed
See detailPrimary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man.
Paolisso, G.; Giugliano, D.; Scheen, André ULg et al

in Acta Endocrinologica (1987), 115(2), 161-9

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 12 (0 ULg)
Peer Reviewed
See detailThe 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.
Castillo, M.; Scheen, André ULg; Paolisso, G. et al

in Acta Endocrinologica (1987), 116(3), 364-72

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 ... [more ▼]

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) [less ▲]

Detailed reference viewed: 18 (0 ULg)