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Biomedical subjects

P Lefèbvre

Publications and source records attributed to P Lefèbvre.

At least 19 recordsLinked to original sources
PubMed1997

Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma.

The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-II protein took the high-molecular-weight form. We also analyzed the parental imprinting status and the promoter usage of the IGF-II gene. Our results showed loss of imprinting (LOI) in the mesothelioma while the imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we analyzed, whereas IGF-II mRNA transcription from promoter P3 was only detected in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the analyzed tissues and cells. The type-I receptor mRNA expression was very low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the mesothelioma, while IGFBP-2, -3 and -5 transcripts were detected in the placenta. IGFBP-1 and -6 transcripts were not detected.

Aged↗
PubMed1997

Acute functional iron deficiency in obese subjects during a very-low-energy all-protein diet.

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone.

Adolescent↗
PubMed1995

Glucose handling, diabetes and ageing.

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

Aging↗
PubMed1992

Insulin effects on glucose kinetics in non-insulin-dependent diabetic patients with secondary failure to hypoglycaemic agents: role of different modes and rates of delivery.

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.

Aged↗
PubMed1992

Effects of mild-to-moderate hyperglycaemia per se on glucose production and uptake in the elderly.

OBJECTIVES: In order to better understand the mechanisms responsible for the diminished glucose tolerance that occurs in the elderly, the present study aimed at investigating the effect of mild hyperglycaemia on glucose production and uptake in a group of aged subjects. For comparison, a group of young subjects was simultaneously investigated. METHODS: Seven aged (71.8 +/- 2.3 yrs) and seven young (25.5 +/- 1.7 yrs) healthy non-obese subjects underwent two hyperglycaemic glucose-clamps having as targets plasma glucose levels 7.5 and 10.0 mmol/L. Contemporary infusion of D-[3-3H]-glucose allowed determination of glucose turnover parameters in basal conditions and during the clamps. Endogenous pancreatic secretion was inhibited by somatostatin (8.3 micrograms/min) while glucagon (67 ng/min) and insulin (0.15 mU/kg/min) were replaced by exogenous infusions. RESULTS: In basal conditions, glucose uptake (12.9 +/- 0.5 vs 14.4 +/- 0.4 mumol/kg/min; p < 0.05) and glucose metabolic clearance rate (2.58 +/- 0.15 vs 3.35 +/- 0.10 ml/kg/min; p < 0.01) were lower in elderly vs young subjects. In the hyperglycaemic glucose-clamps, we observed, in the elderly subjects, the persistence of a greater glucose production during mild (7.5 mmol/L) (11.6 +/- 0.4 vs 9.7 +/- 0.2 mumol/kg/min; p < 0.005) but not moderate (10 mmol/L) (3.5 +/- 0.1 vs 3.4 +/- 0.1 mumol/kg/min; NS) hyperglycaemia. In contrast, glucose-induced glucose uptake and glucose metabolic clearance rate were similarly affected by glucose infusions in both groups of subjects. Moreover, in elderly but not in young subjects, basal glucose disappearance rate was significantly negatively correlated with fasting plasma glucose levels (r = -0.84; p < 0.01). CONCLUSIONS: In the basal state, glucose uptake and glucose metabolic clearance rate are slightly impaired in elderly, compared to young subjects. Furthermore, in the elderly, endogenous glucose production is less suppressed by mild hyperglycaemia i.e. 7.5 mmol/L, than it is in young people. Such impairment in the inhibition of endogenous glucose production is not seen when blood glucose attains 10 mmol/L. We suggest that impairment in glucose tolerance in the elderly results from both reduced glucose uptake (in basal conditions) and excessive glucose production (at mild hyperglycaemic levels).

Adult↗
PubMed1990

Evidence for a hyperglycaemia-dependent decrease of antithrombin III-thrombin complex formation in humans.

In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus.

Adult↗