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W J Malaisse

Publications and source records attributed to W J Malaisse.

At least 19 recordsLinked to original sources
PubMed2002

Underestimation of D-glucose utilisation as judged from the conversion of D-[3-(3)H]glucose to (3)HOH.

AIMS/HYPOTHESIS: The conversion of D-[3-(3)H]glucose to (3) HOH is currently measured to assess D-glucose utilisation. The validity of such a procedure was re-evaluated. METHODS: The conversion of D-[3-(3)H]glucose and D-[5-(3)H]glucose to (3) HOH was measured in rat pancreatic islets, parotid cells and erythrocytes. The tritiation of lipids were also examined in islets exposed to D-[3-(3)H]glucose or D-[5-(3)H]glucose. RESULTS: In rat pancreatic islets and parotid cells, but not in rat erythrocytes, the generation of (3) HOH from D-[3-(3)H]glucose underestimates the rate of D-glucose utilisation, this being apparently attributable to a partial escape from detritiation of [1-(3)H]glycerone-3-phosphate. Such an escape phenomenon resulted in a higher tritiation of lipids in pancreatic islets exposed to D-[3-(3)H]glucose, rather than D-[5-(3)H]glucose. Its relative extent was affected by a number of environmental factors such as the cell type under consideration, the metabolic status of the animals, and the extracellular concentration of D-glucose. CONCLUSION/INTERPRETATION: These findings impose a reservation on the use of D-[3-(3)H]glucose conversion to (3)HOH as a tool to assess the utilisation of the hexose in some cell types.

Amino Acids↗
PubMed2002

Resistance of succinic acid dimethyl ester insulinotropic action to exendin (9-39) amide.

Exendin (9-39) amide (Ex [9-39]) was recently proposed for use in the treatment of alimentary or reactive hypoglycaemia. It was indeed found to antagonise the insulinotropic action of GLP-1 in rats infused with the dimethyl ester of succinic acid (SAD). We have now investigated whether, under comparable experimental conditions, Ex (9-39) also opposes the insulin-releasing action of SAD itself. Since this was not the case, Ex (9-39) could be safely used to abolish the incretin effect of GLP-1 without interfering with the control of insulin secretion by circulating nutrients.

Animals↗
PubMed2001

Pancreatic fate of a (125)I-labelled mouse monoclonal antibody directed against pancreatic B-cell surface ganglioside(s) in control and diabetic rats.

The possible use of a mouse monoclonal antibody directed against rat pancreatic B-cell surface ganglioside(s) and labelled with radioactive iodine for selective imaging of the endocrine pancreas by a non-invasive procedure was investigated by following its pancreatic fate in experiments conducted either in vitro by incubation of rat isolated pancreatic islets, acinar tissue and pancreatic pieces or in vivo after intravenous injection of the (125)I-labelled antibodies ([(125)I]gamma-G). Although the binding of [(125)I]gamma-G per microg protein was about one order of magnitude higher in isolated islets than in acinar tissue, no significant difference was detected when comparing pancreatic pieces or isolated islets from control animals and rats rendered diabetic by one or two prior administrations of streptozotocin (STZ rats). Likewise, except in one set of experiments, no significant difference was found between control animals and STZ rats, when measuring the radioactive content of the pancreatic gland, relative to that of plasma, 1-4 days after the intravenous injection of [(125)I]gamma-G. These findings indicate that under the present experimental conditions, the mouse monoclonal antibody labelled with radioactive iodine does not appear to be a promising tool for selective imaging of the endocrine pancreas, e.g. by single photon emission computerized tomography.

Animals↗
PubMed2001

Pancreatic fate of D-[3H] mannoheptulose.

D-Mannoheptulose was recently postulated to be transported into cells by GLUT2. The validity of such an hypothesis was assessed by comparing the uptake of tritiated D-mannoheptulose by pancreatic islets versus pieces of pancreas and, in the latter case, by comparing results obtained in control rats versus animals injected with streptozotocin (STZ). The uptake of D-[3H] mannoheptulose by islets represents a time-related and temperature-sensitive process, inhibited by cytochalasin B and enhanced by D-glucose. The uptake of the tritiated heptose was much lower in pieces of pancreatic tissue and inhibited by D-glucose, at least in the STZ rats. Whether in pieces of pancreas exposed in vitro to D-[3H] mannoheptulose or after intravenous injection of the tritiated heptose, the radioactive content of the pancreatic tissue was lower in STZ rats than in control animals. This contrasted with an unaltered radioactive content of liver and muscle in the STZ rats, at least when treated with insulin. Suitably radiolabelled D-mannoheptulose or an analogue of the heptose could thus conceivably be used for quantification of the endocrine pancreatic mass.

Animals↗
PubMed2001

On the track to the beta-cell.

The imaging and quantification of the endocrine pancreas by a non-invasive procedure remains a challenge. In the prolongation of prior work on selected succinic acid esters and monosaccharide esters, it is proposed that D-mannoheptulose, which might be transported across the plasma membrane at the intervention of GLUT-2, could be used to label preferentially the endocrine moiety of the pancreatic gland. This heptose is taken up more efficiently by hepatocytes and islet cells, than by erythrocytes, parotid cells, acinar pancreatic cells or tumoural islet cells of either the RINm5F or INS-1 line. Likewise, D-mannoheptulose only inhibits D-glucose metabolism in hepatocytes and isolated islets. Its hexaacetate ester, however, inhibits the catabolism of the hexose in all cell types. The uptake of D-mannoheptulose represents a carrier-mediated process. Human islets behave like rat islets in terms of D-mannoheptulose uptake and inhibition by the heptose of both D-glucose metabolism and insulinotropic action. The use of radiolabelled analogs of D-mannoheptulose suitable for imaging of the endocrine pancreas is discussed. In the same perspective, it is proposed that advantage could be taken of the much greater accumulation of glycogen in insulin-producing cells, as compared to other pancreatic cell types, in situations of sustained hyperglycaemia.

Animals↗
PubMed2001

Pancreatic and hepatic glycogen content in normoglycemic and hyperglycemic rats.

As judged from morphological criteria, glycogen accumulates to a larger extent in insulin-producing B-cells than in acinar cells of the pancreas in situations of sustained hyperglycemia. In the present study, the glycogen content of the pancreatic gland and liver was measured in either euglycemic or glucose-infused hyperglycemic control rats, as well as in streptozotocin-induced diabetic rats. Whilst the glycogen content of the pancreas was significantly higher in STZ rats than in control euglycemic rats, it was further enhanced in glucose-infused control rats, despite the fact that the latter animals were not more severely hyperglycemic and for a shorter time than STZ rats. From these measurements, it was estimated that, relative to wet weight, the glycogen content was, under the present experimental conditions, about 75 times higher in insulin-producing than other pancreatic cells. Moreover, it is proposed that the intravenous administration of glucagon may help in distinguishing between the glycogen present in the endocrine and exocrine moieties of the pancreatic gland, this hormone being apparently unable to provoke glycogenolysis in the exocrine pancreas, at variance with the situation prevailing in isolated pancreatic islets.

Aminoglycosides↗
PubMed2001

Effects of D-mannoheptulose upon D-glucose metabolism in tumoral pancreatic islet cells.

D-[3H]mannoheptulose was recently reported to be poorly taken up by tumoral pancreatic islet cells of the RINm5F and INS-1 lines. We have now investigated the effects of D-mannoheptulose upon D-glucose metabolism in these two cell lines. D-mannoheptulose (1.0-10.0 mM) only caused a minor decrease of D-glucose metabolism in RINm5F cells, whether at low (1.1 mM) or higher (8.3 mM) D-glucose concentration. A comparable situation was found in INS-1 cells examined after more than 20 passages. In both cases, however, the hexaacetate ester of D-mannoheptulose (5.0 mM) efficiently inhibited D-glucose metabolism. In the INS-1 cells, the relative extent of the inhibitory action of D-mannoheptulose upon D-glucose metabolism increased from 12.4 +/- 2.6 to 38.3 +/- 3.8% as the number of passages was decreased from more than 20 to 13-15 passages, the latter percentage remaining lower, however, than that recorded in INS-I cells also examined after 13-15 passages but exposed to D-mannoheptulose hexaacetate (66.9 +/- 2.2%). These findings when compared to our recent measurements of D-[3H]mannoheptulose uptake, reinforce the view that the entry of the heptose into cells and, hence, its inhibitory action on D-glucose metabolism are dictated by expression of the GLUT2 gene.

Animals↗
PubMed2001

Oxidation of D-[U-(14)C] glucose and [1,12-(14)C] dodecanedioic acid by pancreatic islets from Goto-Kakizaki rats.

In pancreatic islets from hereditarily diabetic GK rats, [1,12 -(14)C] dodecanedioic acid (5.0 mM) was oxidized at a rate representing about 5 % of that of D-[U - (14)C] glucose (8.3 mM). Dioic acid and hexose failed to exert any significant reciprocal effects on their respective oxidation. The production of (14)CO(2) from [1,12 -(14)C] dodecanedioic acid was proportional to its concentration in the 0.2 - 5.0 mM range. These results were essentially comparable to those obtained in islets from control rats. They extend, therefore, to GK rats the knowledge that dodecanedioic acid acts as a nutrient in pancreatic islet cells.

Animals↗
PubMed2001

Assessment of islet beta-cell mass in isolated rat pancreases perfused with D-[(3)H]mannoheptulose.

D-mannoheptulose is apparently transported into cells mainly at the intervention of GLUT-2 and hence was recently proposed as a tool to label preferentially insulin-producing beta-cells in the pancreatic gland. The validity of such a proposal was investigated in the present study conducted in isolated perfused pancreatic glands from control and streptozotocin-induced diabetic rats. After a 30-min equilibration period, D-[(3)H]mannoheptulose (0.1 mM) and [U-(14)C]sucrose (0.5 mM) were infused for 15 min in the presence of 30 mM D-glucose. The pancreatic glands were then perfused for 10 min with a nonradioactive medium during and after administration of cytochalasin B (0.02 mM). Under these experimental conditions, the intracellular distribution space of D-[(3)H]mannoheptulose averaged 5.42 +/- 0.75 nl/mg in control animals, whereas it failed to be significantly different from zero in the streptozotocin rats. The present procedure may thus allow the assessment of the relative contribution of islet beta-cells to the total mass of the pancreatic gland.

Animals↗
PubMed2001

Glycogen accumulation in rat pancreatic islets: in vitro experiments.

Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic islets, but not so in acinar pancreatic cells. Advantage conceivably could be taken from such a situation in the perspective of the noninvasive imaging of the endocrine pancreas. The present experiments aim, therefore, at characterizing the time course for glycogen accumulation in pancreatic islets cultured at a high concentration (30 mM) of D-glucose in the presence of tracer amounts of either D-[U-14C]glucose or 2-deoxy-2-[18F]fluoro-D-glucose. The 14C-labeled glycogen content of the cultured islets increased with time (150 min to 72 h), exceeded that found in acinar tumoral cells, and did not decrease over 60 min of incubation at 30 mM D-glucose in the absence of D-[U-14C]glucose. Glycogenolysis was observed, however, when the concentration of D-glucose was decreased to 2.8 mM and, in such a case, was further enhanced by forskolin and theophylline. Such a glycogenolysis coincided with the generation of 14CO2 from radioactive intracellular precursors and alteration of the B-cell secretory response to D-glucose. The radioactive glycogen content was higher in islets exposed to 2-deoxy-2-[18F]fluoro-D-glucose than D-[U-14C]glucose. Prior exposure of the islets to streptozotocin suppressed the accumulation of glycogen during their subsequent culture at high D-glucose concentration. These findings may help to define the experimental conditions optimal for the labeling and accumulation of islet glycogen in vivo.

Amino Acids↗
PubMed2001

Labeling of pancreatic glycogen by D-[U-14c]glucose in hyperglycemic rats.

Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic islets, but not so in acinar pancreatic cells. We investigated whether advantage could be taken of such a situation in the perspective of the noninvasive imaging of the endocrine pancreas. Control rats or animals injected with streptozotocin (STZ) were infused with solutions of D-glucose mixed with a tracer amount of D-[U-14C]glucose, and the radioactive glycogen content of both liver and pancreas was then measured. After 48 h of infusion, the radioactive glycogen content of the pancreas was 30 times lower in STZ rats than in control animals, coinciding with a 50 times lower insulin content. In the control rats, a sizable labeling of pancreatic glycogen was also recorded when D-[U-14C]glucose was infused for only the last 4 h of unlabeled D-glucose infusion; such a labeling was not decreased when the animals were further infused for 1 h with only the unlabeled hexose. Moreover, a pronounced difference in the pancreatic gland and blood radioactive content of control rats was still observed when the hyperglycemic animals were killed only 40 min after the i.v. injection of D-[U-14C]glucose. In STZ rats transplanted with islets and later infused with D-[U-14C]glucose, the total radioactive content and radioactive glycogen content were both much higher in the transplanted islets than in the pancreatic gland. These results allow one to define the conditions under which the administration of either 2-deoxy-2-[18F]fluoro-D-glucose or 11C-labeled D-glucose could conceivably be used to favor the selective labeling of the endocrine, as distinct from exocrine, pancreas.

Animals↗
PubMed2001

Suppression by exendin(9-39)amide of glucagon-like peptide-1 insulinotropic action in rats infused with dimethyl ester of succinic acid.

Glucagon-like peptide-1 (GLP-1) acts as a nutrient-dependent insulin-releasing agent, and its insulinotropic action is enhanced by nutrient secretagogues, such as the dimethyl ester of succinic acid (SAD). In the present study, a primed constant infusion of SAD (0.5 micromol followed by 0.25 micromol/min both per g of body wt) was found to increase plasma insulin concentration in fed anesthetized rats, to potentiate the B-cell secretory response to GLP-1 (0.5 pmol/g of body wt), and to unmask the hypoglycemic potential of the gastrointestinal hormone. In the SAD-infused rats, the infusion of exendin(9-39)amide (5.0 pmol/min per g of body wt), 1 min before and 3 min after GLP-1 injection, decreased plasma insulin concentration before GLP-1 injection, suppressed the B-cell secretory response to GLP-1, and both delayed and minimized its hypoglycemic action. It is proposed, therefore, that exendin (9-39)amide could represent a tool in the treatment of alimentary or reactive hypoglycemia.

Animals↗
PubMed2001

Potentiation and prolongation of the insulinotropic action of glucagon-like peptide 1 by methyl pyruvate or dimethyl ester of L-glutamic acid in a type 2 diabetes animal model.

Methyl pyruvate and the dimethyl ester of L-glutamic acid were administered intravenously, as a primed constant infusion (1.0-2.0 micromol followed by 0.5-1.0 micromol/min, both expressed per gram of body wt), in adult rats that had been injected with streptozotocin during the neonatal period. Each ester augmented plasma insulin concentration and potentiated and/or prolonged the insulinotropic action of glucagon-like peptide 1 (GLP-1) injected intravenously (5 pmol/g of body wt) at min 5 of the test. It is proposed, therefore, that suitable nonglucidic nutrients, susceptible to bypassing the site-specific defects of D-glucose transport and metabolism responsible for the preferential impairment of the B-cell secretory response to D-glucose in non-insulin-dependent diabetes, could be used to optimize the insulinotropic action of GLP-1.

Animals↗
PubMed2001

Pancreatic glycogen content in Goto-Kakizaki rats.

In situations of sustained hyperglycemia, much larger amounts of glycogen accumulate in islet B-cells than in other pancreatic cells. The labelling of such a glycogen pool could thus conceivably provide a mean for assessing the relative contribution of insulin-producing cells to the total pancreatic mass. In such a perspective, the present study aims at investigating pancreatic glycogen accumulation in hereditarily diabetic Goto-Kakizaki (GK) rats. When cultured at 30 mM D-glucose in the presence of D-[U-14C]glucose, pancreatic islets from GK rats accumulated 14C-labelled glycogen in a manner comparable to that previously documented in islets from normal rats. Likewise, the glycogen content of the pancreatic gland, relative to the plasma D-glucose concentration, was not different in GK and normal rats. The GK rats thus apparently represent a suitable model for further studies on the in vivo labelling of B-cell glycogen in the perspective of the non-invasive imaging and quantification of the endocrine pancreas.

Animals↗
PubMed2001

D-mannoheptulose phosphorylation by hexokinase isoenzymes.

D-mannoheptulose is a specific inhibitor of D-glucose phosphorylation by hexokinase isoenzymes. In the present study, the phosphorylation of this heptose was investigated by either a spectrophotometric or radioisotopic procedure. Using yeast hexokinase, the phosphorylation of 25 mM D-mannoheptulose only represented 0.02% of that of 5 mM D-glucose. Such a percentage was increased to 3.93% in the case of bovine heart hexokinase. In the latter case, the Km for D-mannoheptulose was close to 0.2 mM and both D-glucose (0.1-1.0 mM) and D-glucose 6-phosphate (also 0.1-1.0 mM) inhibited the phosphorylation of the heptose (0.03-0.60 mM). Human B-cell glucokinase also catalyzed the phosphorylation of D-mannoheptulose (0.1 mM), which was now increased in a bell-shaped manner by D-glucose (1.0-20 mM). Likewise, rat parotid gland, liver and pancreatic islet homogenates catalyzed the phosphorylation of D-[3H]mannoheptulose. The results obtained in these three tissues differed from one another by their absolute values (per mg wet wt.), relative values (by reference to the phosphorylation rate of 10 mM D-glucose), and sensitivity to inhibition by D-glucose (10 mM).

Amino Acid Substitution↗
PubMed2001

Uptake of 1-deoxy-1-[125I]iodo-D-mannoheptulose by different cell types: in vitro and in vivo experiments.

D-mannoheptulose was recently proposed as a tool to label preferentially insulin-producing cells in the pancreatic gland in the perspective of the non-invasive imaging of the endocrine pancreas. In such a perspective, we have now synthesized 1-deoxy-1-[125I]iodo-D-mannoheptulose ([125I]MH) and examined its uptake by different rat cell types. No phosphorylation of [125I]MH by bovine heart hexokinase could be detected. The apparent distribution space of [125I]MH largely exceeded that of [U-14C]sucrose, considered as an extracellular marker, in erythrocytes, parotid cells, hepatocytes, pancreatic pieces and isolated pancreatic islets. Relative to the mean intracellular distribution space of 3HOH, that of [125I]MH was not significantly different in pancreatic pieces from either normal rats or streptozotocin-induced diabetic animals (STZ rats). In pancreatic islets, the uptake of [125I]MH was decreased at low temperature, but failed to be significantly affected by cytochalasin B. Sixty min after the intravenous injection of [125I]MH, the radioactive content of selected organs displayed the following hierarchy: muscle<pancreas<liver<parotid<kidney<plasma. In this respect, there was no obvious difference between control and STZ rats. Taken as a whole, these findings suggest that 1-deoxy-1-[125I]iodo-D-mannoheptulose does not display the same specificity towards GLUT2, as that previously documented in the case of D-[3H]- mannoheptulose.

Animals↗