Biomedical subjects

P Poucheret

Publications and source records attributed to P Poucheret.

10 recordsLinked to original sources

PubMed2002

Influence of food and diabetes on pharmacokinetics of sodium tungstate in rat.

In this paper, the influence of food and diabetes on the pharmacokinetics of sodium tungstate in rat was investigated. The compound was administered intravenously (9 mg/kg) and orally in the form of solution (36 mg/kg). An empirical Bayes methodology was used to compute individual pharmacokinetic parameters. Sodium tungstate followed first-order kinetics, and plasma concentration versus time data were described by a two-compartment model. A significant relationship was found between the bioavailability and the status of the animals. Total plasma clearance and elimination half-life averaged 3.1 ml/min/kg and 1.6 h, respectively. Food had some effects on the extent of sodium tungstate absorption. After oral administration, the bioavailability (0.67 versus 0.85), C(max) (6.10 versus 15.2 microg/ml) and AUC (70.7 versus 105 mgh/l) were 20, 60 and 32% lower in fed than in fasted rats, respectively. The presence of cellulose and sulphate anions in rat chow could partially explain the fed state-associated reduction of tungstate bioavailability. In streptozotocin-induced diabetic fed rats, a 25% decrease occurred in AUC and F, and a 14% increase occurred in the elimination rate constant compared with healthy fed rats. These changes could be explain on the one hand, by the increase of liquid consumption and food intake, and on the other hand, by a gastroparesis in the early diabetic rats.

Animals↗

PubMed2001

Antioxidant capacities and phenolics levels of French wines from different varieties and vintages.

Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (-)-epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French varietal commercial wines taken from southern France to study the antioxidant capacity and the daily dietary intake of these compounds for the French population. The highest antioxidant capacity was obtained with red wines and ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines, Chardonnay enriched in phenolics by special wine-making was found to have an antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines classified by vintages (1996-1999) antioxidant capacities were approximately 20 mmol/L and then decreased to 13.4 mmol/L for vintages 1995-1991. Sweet white wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines (1.91 mmol/L). On the basis of a still significant French wine consumption of 180 mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2, B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rosé wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic) mg/day/resident for the French population. Red wine, and particularly Pinot Noir, Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched in phenolics during wine-making for white varieties contribute to a very significant catechin dietary intake.

Anthocyanins↗

PubMed2000

Pharmacokinetics of sodium tungstate in rat and dog: a population approach.

Sodium tungstate has been found to correct hyperglycemia in insulin- and noninsulin-dependent models of diabetes when administered in drinking fluid with a low degree of toxicity; thus, it provides a potential treatment for diabetes. In the present report, pharmacokinetic studies with sodium tungstate were carried out in the Sprague-Dawley rat and beagle dog. This drug was administered either i.v. (8.97 mg/kg in rat; 25 and 50 mg/kg in dog) or orally in the form of solution (35.9 and 107.7 mg/kg in rat; 25 and 50 mg/kg in dog). Tungsten was quantified using an inductively coupled plasma method. Pharmacokinetic parameters were estimated using a population approach. Sodium tungstate followed first order kinetics, and plasma concentration-versus-time data were adequately described by a two-compartment model. In rat, bioavailability was high (92%), whereas it was lower in dog (approximately 65%). The total volume of distribution expressed by unit of body weight was much higher when the animal was smaller (0.46 l/kg in rat versus 0.23 l/kg in dog). The total body clearance normalized by weight, 0.19 l/h/kg in rat versus 0.043 l/h/kg in dog, changed as for the volume of distribution. The elimination half-life was two times higher in dog (approximately 4 h) than in rat (approximately 1.7 h). In the range of 35.9 to 107.7 mg/kg after oral administration in rat and 25 to 50 mg/kg after oral and i.v. administration in dog, tungsten plasma concentrations increased in proportion to dose.

Administration, Oral↗

PubMed2000

[Vanadium and diabetes: pancreatic and peripheral insulinomimetic properties] [In Process Citation]

A very large body of research has been devoted to diabetes mellitus with the goal of better understanding this complex disease for better patient treatment. Pathophysiological research in the rat has focused on Pharmacological research suggests that vanadium could be a possible therapeutic agent due to its activity on insulin secretion and its peripheral insulinomimetic properties. Results suggest that the antidiabetic properties of vanadium result from Vanadium derivatives thus comprise a novel class of compounds with promising therapeutic potential and favorable pharmacokinetic properties (oral administration).

Journal Article↗

PubMed1999

Effects of bis(maltolato) oxovanadium (IV) on protein serine kinases in skeletal muscle of streptozotocin-diabetic rats.

The in vivo effects of bis(maltolato)oxovanadium (IV) (BMOV) on the activity of protein serine kinases in skeletal muscle of STZ-diabetic Wistar rats were studied. BMOV was administered to STZ-diabetic rats at a concentration of 0.75 mg/ml for 8 weeks. Chronic BMOV treatment completely normalized plasma glucose levels in the diabetic animals after 8 weeks of treatment. Insulin-stimulated ERK-1 and ERK-2 activity was markedly increased in STZ-diabetic rats. Chronic BMOV treatment normalized the activity of ERK-2 in the diabetic treated animals, whereas the activity of ERK-1 was unaffected. In contrast to ERK-1 and ERK-2, the activity of the ribosomal S6 kinase p90rsk was decreased in STZ-diabetic rats. BMOV treatment restored the activity to normal levels. Basal p70 S6K activity was increased about 2.5-fold in the untreated diabetic group and no further increase in activity was observed after insulin stimulation. BMOV treatment did not correct the changes in p70 S6K activity in either the basal or insulin-stimulated states. In conclusion (i) the activity of ERK-1, ERK-2 and p90rsk were altered in skeletal muscle of STZ-diabetic rats; (ii) the glucoregulatory effects of BMOV were accompanied by concurrent improvement in the activities of ERK-2 and p90rsk; and (iii) there appears to be a dissociation between the activation of ERK-2 and p90rsk, suggesting that the regulation of p90rsk may be much more complex in vivo.

Animals↗

PubMed1998

Insulin-induced Glut4 recruitment in the fatty Zucker rat heart is not associated with changes in Glut4 content in the intracellular membrane.

Impaired cardiac glucose metabolism and glucose transport have been shown in the insulin resistant fatty Zucker rat. The aim of the present study was to examine the translocation of the insulin-sensitive glucose transporter (Glut4) in the heart of the fatty Zucker rat under in vivo conditions. Insulin was injected into both lean (FA/?) and fatty (fa/fa) Zucker rats via the tail vein. The time course of cardiac Glut4 translocation was studied by determining the subcellular distribution of Glut4 using a newly developed ELISA quantitation method. Insulin (10 U/kg) caused a 30% and 37% increase in plasma membrane Glut4 content at 20 min after injection in lean and fatty rats respectively. The plasma membrane Glut4 contents in the basal and insulin-stimulated states were significantly lower in the fatty rat when compared to the lean control. The dose effect of insulin (2.5-10 U/kg) on Glut4 mobilization to the plasma membrane was similar in both phenotypes. The time course of Glut4 mobilization to the plasma membrane (5-30 min), which was similar in both lean and fatty Zucker rats, showed that maximal translocation was reached at 5 min post insulin injection and persisted throughout the remaining 25 min. However, in fatty Zucker rats, Glut4 content in the intracellular membrane remained unchanged at all insulin doses and all time points studied. Collectively, these results show that Glut4 recruitment to the plasma membrane is responsive to insulin in the fatty Zucker rat heart and that the maximal response was similar to that in lean Zucker rats. However, the recruitment of Glut4 to the plasma membrane was not associated with changes in the intracellular membrane Glut4 content.

Animals↗

PubMed1998

Vanadyl treatment normalizes submandibular salivary gland insulin-like immunoreactivity in streptozotocin-diabetic rats.

Rat submandibular salivary glands (SSG) contain a compound displaying insulin-like immunoreactivity (ILI) and various biological activities of insulin. As SSG ILI levels were reported to be increased in streptozotocin (STZ)-induced diabetes but not normalized by a two-week insulin treatment, we decided to check whether another antidiabetic treatment, vanadyl sulphate (VOSO4), was able to regulate SSG ILI concentration. A short term (8 days) i.p. VOSO4 treatment (total dose = 1.3 mmol/kg) of rats made diabetic 8 days earlier by a single i.v. injection of STZ (60 mg/kg BW) was able to induce a long-term (4 weeks) correction of hyperglycemia while weight gain was re-established. In untreated diabetic animals (approximately -25%) and increased (approximately +175%) as compared to normal rats. Both parameters were normalized in VOSO4-treated diabetic rats.

Animals↗

PubMed1998

Vanadium and diabetes.

We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-term effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanadium compounds. One of these, bismaltolato-oxovanadium IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadium is a phosphatase inhibitor and that vanadium can activate serine/threonine kinases distal to the insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.

Animals↗

PubMed1996

Vanadyl sulphate differently influences insulin response to glucose in isolated pancreas of normal rats after in vivo or in vitro exposure.

The effect of the antidiabetic agent vanadyl sulphate (VOSO4) on the endocrine pancreas function of normal rats was studied using the isolated pancreas preparation. A short-term (8 days) i.p. treatment (15 mg/kg per day) resulted in attenuation of high glucose-stimulated insulin release, at day 9 but also at days 19, i.e., after full recovery of appetite and weight, while blood and pancreas vanadium concentrations were still elevated. Six months of oral VOSO4 treatment (0.75 mg/ml in drinking water) resulted in elevated vanadium concentrations while glucose-stimulated insulin release was attenuated as compared to pair-fed animals. Conversely, when directly perfused in pancreas, VOSO4 potentiated glucose-stimulated insulin release. These apparently opposite effects may be related to the ability of VOSO4 to exert both peripheral insulinomimetic effects-leading to chronic reduction in insulin demand-, and a direct pancreatic insulinotropic activity.

Administration, Oral↗

PubMedDate not supplied

Long-term correction of STZ-diabetic rats after short-term i.p. VOSO4 treatment: persistence of insulin secreting capacities assessed by isolated pancreas studies.

We have previously shown that 3 week oral VOSO4 treatment of streptozotocin (STZ, 60 mg/kg)-induced diabetic rats was able to correct diabetes for 13 weeks after treatment withdrawal. In the present study, we investigated whether a short-term (8 days) i.p. VOSO4 treatment was similarly able to reverse the diabetic state. Insulin secretory capacities were assessed at distance of treatment using the isolated pancreas preparation. Seven treatment-groups were performed: high dose VOSO4-treated diabetics (HVD, 1.3 mM/kg/8 days), food-restricted diabetics (FRD, food adjusted to HVD levels), low dose VOSO4-treated diabetes (LVD, 0.06 mM/kg/day), insulin-treated diabetics (ID, dose adjusted to normalize glycaemia) and VOSO4 (0.06 mM/kg/day) + insulin (dose adjusted to normalize glycaemia in the presence of vanadium)-treated diabetics (IVD), in addition to the corresponding untreated non-diabetic controls (C) and diabetics (D). Our results indicate that long-term correction of diabetes (a) can be obtained after an 8 day treatment using i.p. VOSO4 in diabetic animals retaining some degree of pancreatic function, (b) is not obtained with insulin treatment or food restriction although the association of VOSO4 and insulin was found beneficial, (c) can be prolonged in some individuals for at least 4 months, i.e. in conditions such that tissue vanadium concentrations had returned to values close to pre-treatment levels, (d) is associated with improved and in some cases normalized insulin secretion from isolated pancreas. The protective or corrective role of VOSO4 on diabetes-related pancreatic alterations, as well as the potential of the VOSO4-insulin association should be further studied in view of the possible use of vanadium derivatives in the treatment of diabetes.

Animals↗