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Peer Reviewed
See detailInsulin and metabolic abnormalities in children and family history of NIDDM. The Belgian Luxembourg Child Study.
Guillaume, Michèle ULg; Lapidus, L.; Beckers, F. et al

in International Diabetes Epidemiology Group, Official Satellite Symposium of the 15th IDF Congress (1994)

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See detailInsulin clearance during hyper-insulinemia euglycemia therapy
Penning, Sophie ULg; MASSION, Paul ULg; Pretty, Christopher ULg et al

in Proceedings of the 11th Belgian Day on Biomedical Engineering (2012, December)

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See detailInsulin clearance during hyper-insulinemia euglycemia therapy
Penning, Sophie ULg; MASSION, Paul ULg; Pretty, Christopher ULg et al

Poster (2012, December)

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See detailInsulin Detemir in the Treatment of Type 1 and Type 2 Diabetes
Philips, J. C.; Scheen, André ULg

in Vascular Health and Risk Management (2006), 2(3), 277-83

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain ... [more ▼]

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients. [less ▲]

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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 ▲]

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See detailInsulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1.
Peers, Bernard ULg; Sharma, S.; Teitelman, G. et al

in Molecular Endocrinology (1994), 8(12), 1798-806

The development of endocrine cell types within the pancreas is thought to involve the progressive restriction of pluripotential stem cells, which gives rise to the four major cell types: insulin ... [more ▼]

The development of endocrine cell types within the pancreas is thought to involve the progressive restriction of pluripotential stem cells, which gives rise to the four major cell types: insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-expressing cells. The mechanism by which these peptide hormone genes are induced and then either maintained or repressed during development is unknown, but their coexpression in early precursor cells suggests the involvement of common regulatory factors. Here we show that the somatostatin transcription factor STF-1 is also a principal regulator of insulin expression in beta-cells of the pancreas. STF-1 stimulates the insulin gene by recognizing two well defined islet-specifying elements on the insulin promoter and by subsequently synergizing in trans with the juxtaposed helix-loop-helix protein E47. Within the STF-1 protein, an N-terminal trans-activation domain functions cooperatively with E47 to stimulate insulin transcription. As truncated STF-1 polypeptides lacking the N-terminal activation domain strongly inhibit insulin promoter activity in beta-islet cells, our results suggest that the specification of islet cell types during development may be in part determined by the expression of STF-1 relative to other islet cell factors. [less ▲]

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See detailInsulin induces opposite changes in plasma and erythrocyte magnesium concentrations in normal man.
Paolisso, G.; Sgambato, S.; Passariello, N. et al

in Diabetologia (1986), 29(9), 644-7

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic ... [more ▼]

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic glucose clamp. At min 180 and 210 of the oral glucose tolerance test, a significant decline in plasma magnesium levels (p less than 0.01 and p less than 0.05 respectively) and a significant increase in erythrocyte magnesium levels (p less than 0.01 and p less than 0.05 respectively) were observed. Similar changes were seen during the second hour of the glucose clamp, during which euglycaemia (4.1 +/- 0.4 mmol/l) was maintained despite hyperinsulinaemia (110-130 mU/l). During in vitro incubations, glucose (5 mmol/l) did not modify erythrocyte magnesium levels. In contrast, erythrocyte magnesium levels were significantly increased (p less than 0.01) by insulin (100 mU/l), an effect entirely abolished by ouabain (5 X 10(-4) mol/l). These results suggest that insulin induces a shift of magnesium from the plasma to the erythrocytes both in vivo and in vitro. These data may help to interprete the abnormalities in magnesium circulating levels frequently reported in diabetic patients. [less ▲]

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See detailInsulin Kinetics during Hyper-Insulinemia Euglycemia Therapy (HIET)
Penning, Sophie ULg; MASSION, Paul ULg; Le Compte, Aaron J. et al

in Proceedings of the 8th IFAC Symposium on Biological and Medical Systems (2012, August)

Hyper-insulinemia euglycemia therapy (HIET) is a supra-physiological insulin dosing protocol used in acute cardiac failure to reduce dependency on inotropes to augment or generate cardiac output, and is ... [more ▼]

Hyper-insulinemia euglycemia therapy (HIET) is a supra-physiological insulin dosing protocol used in acute cardiac failure to reduce dependency on inotropes to augment or generate cardiac output, and is based on the inotropic effects of insulin at high doses up to 45-250x normal daily dose. Such high insulin doses are managed using intravenous glucose infusion to control glycemia and prevent hypoglycemia. However, both insulin dosing and glycemic control in these patients is managed ad-hoc. This research examines a selection of clinical data to determine the effect of high insulin dosing on renal clearance and insulin sensitivity, to assess the feasibility of using model-based methods to control and guide these protocols. The results show that the model and, in particular, the modeled renal clearance constant are adequate and capture measured data well, although not perfectly. Equally, insulin sensitivity over time is similar to broader critical care cohorts in level and variability, and these results are the first time they have been presented for this cohort. While more data is needed to confirm and further specify these results, it is clear that the model used is adequate for controlling HIET in a model-based framework. [less ▲]

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See detailInsulin Kinetics during Hyper-Insulinemia Euglycemia Therapy (HIET)
Penning, Sophie ULg; MASSION, Paul ULg; Le Compte, Aaron J. et al

Conference (2012, August)

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See detailInsulin lispro (Humalog) in the treatment of diabetes mellitus: overview of belgian clinical data from global studies.
Bex, M.; Buysschaert, M.; De Leeuw, I. et al

in Acta Clinica Belgica (1999), 54(5), 241-5

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See detailInsulin oscillations per se do not affect glucose turnover parameters in normal man.
Paolisso, G.; Scheen, André ULg; Verdin, Emeline ULg et al

in Journal of Clinical Endocrinology and Metabolism (1986), 63(2), 520-5

To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous ... [more ▼]

To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous pancreatic hormone secretion was inhibited by a somatostatin infusion and glucagon was replaced by continuous glucagon infusion. The two tests were performed at 1-week intervals, during which human insulin was infused either continuously at a constant rate of 0.2 mU kg-1 min-1 or in a pulsatile manner at a rate of 1.3 mU kg-1 min-1 with a switching on/off length of 2/11 min. Blood glucose levels and glucose infusion rates (GIR) were continuously monitored, and glucose turnover was estimated using a [3H]glucose infusion. In both tests, plasma C-peptide dropped markedly, whereas plasma glucagon levels were about twice basal values. Plasma insulin averaged 7 mU liter-1 during continuous infusion and oscillated between 1.5 and 35 mU liter-1 during pulsatile delivery. During the first 30-60 min of both tests, the glucose appearance rate and endogenous glucose production (EGP) increased, resulting in moderate hyperglycemia, which completely suppressed GIR. During the last 65 min, EGP declined, while the glucose disappearance rate and the glucose MCR increased, so that GIR increased progressively to maintain the blood glucose clamped at about 5 mmol liter-1. During this period, no significant differences were found between the two modes of insulin administration for any of the parameters studied. Thus, continuous and pulsatile insulin iv infusion, resulting in physiological peripheral plasma insulin levels, altered the glucose turnover parameters equally, in particular inhibiting EGP, which was stimulated by glucagon during the first part of the study, and stimulating peripheral glucose uptake at the end of the study period. [less ▲]

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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

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See detailInsulin secretion, clearance and action before and after gastroplasty in severely obese subjects.
Letiexhe, Michel ULg; Scheen, André ULg; Gerard, Pascale ULg et al

in International Journal of Obesity & Related Metabolic Disorders (1994), 18(5), 295-300

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A ... [more ▼]

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTT, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG when compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53,125 +/- 7968 to 42,302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53,626 +/- 6378 to 21,111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailInsulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.
Letiexhe, Michel ULg; Scheen, André ULg; Gerard, Pascale ULg et al

in Journal of Clinical Endocrinology and Metabolism (1993), 77(5), 1263-8

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test ... [more ▼]

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations. [less ▲]

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See detailInsulin secretion, metabolism and sensitivity before and after a protein-sparing modified fast in obese subjects.
Paquot, Nicolas ULg; Scheen, André ULg; juchmes, Jacques et al

in Diabetologia (1990), 33(suppl), 216

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See detailInsulin Sensitivity during Hypothermia in Critically Ill Patients
Sah Pri, Azurahisham; Chase, J. Geoffrey; Le Compte, Aaron J. et al

Poster (2013, September)

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See detailInsulin sensitivity in anorexia nervosa: a mirror image of obesity?
Scheen, André ULg; Castillo, M.; Lefebvre, Pierre ULg

in Diabetes/Metabolism Reviews (1988), 4(7), 681-90

Although, in many respects and from a metabolic point of view, obesity and AN are clearly two opposite pathological conditions, the available data concerning insulin sensitivity in these two syndromes are ... [more ▼]

Although, in many respects and from a metabolic point of view, obesity and AN are clearly two opposite pathological conditions, the available data concerning insulin sensitivity in these two syndromes are not so obviously opposite. Indeed, whereas everybody is convinced that obesity is characterized by an increased insulin resistance, the papers reporting insulin sensitivity parameters in AN contain some apparently contradictory results. The observations of simultaneously low fasting blood glucose and plasma-insulin levels in anorectic patients could suggest increased insulin sensitivity in AN. However, if this is the case, it would be present despite other metabolic and hormonal changes (increased plasma concentrations of free fatty acids, cortisol, and growth hormone) which are known factors of insulin resistance. During an oral glucose-tolerance test, an impaired glucose-tolerance occurring despite sustained insulin response to glucose is usually found in anorectic patients before treatment; these abnormalities are, at least partially, reversed after successful refeeding. From these results, such conclusive, if indirect, evidence exists for relative insulin insensitivity in untreated AN. Similar results were initially reported with the intravenous glucose-tolerance test. Typically, the coefficient of glucose assimilation K was reduced in anorectic patients before treatment and increased after realimentation. This seemed to occur despite a relative increase in insulin response to glucose, which again may be related to insulin resistance in these undernourished subjects. However, more recent data demonstrated that the early insulin response is significantly lower in anorectic patients than in controls and that more than half of these patients have normal glucose-tolerance despite decreased peripheral plasma insulin levels. These latter observations, on the contrary, suggest an increased insulin sensitivity, at least in some patients with AN. Only the recently developed minimal model method allows us to discriminate between changes in insulin secretion and action after intravenous glucose injection and thus to infer accurately the sensitivity of the tissues to insulin. Unfortunately, this technique has not been applied to anorectic patients, until now, to solve the controversy. The simplest way to assess the action in vivo of insulin is to perform an intravenous insulin-tolerance test. However, the initial findings with this test, which showed exaggerated fall in plasma-glucose values and delayed return to basal levels after intravenous injection of insulin in AN, do not necessarily mean increased insulin sensitivity in these self-starved patients.(ABSTRACT TRUNCATED AT 400 WORDS) [less ▲]

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