Phytochemical screening and free radical scavenging activity of Citrullus colocynthis seeds extracts.

Objective: To study the phytochemical screening of different extracts from Citrullus colocynthis (C. colocynthis ) seeds extracts and to assess their antioxidant activity on the DPPH free radical scavenging.

Methods: Phytochemical screening, total content of polyphenols and flavonoids of C.

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.

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.

Uptake of D-mannoheptulose by rat erythrocytes, hepatocytes and parotid cells.

D-[3H]mannoheptulose (or D-[1-14C] mannoheptulose) net uptake was measured in rat erythrocytes, parotid cells and hepatocytes. In the erythrocytes and parotid cells, the intracellular distribution space of the heptose (0.1 mM) represented only about 1 and 13%, respectively, of the intracellular 3HOH space.

Uptake of D-mannoheptulose by normal and tumoral pancreatic islet cells.

D-mannoheptulose was recently proposed as a possible tool to label preferentially insulin-producing cells in the pancreatic gland. In the present study, D-[3H]-mannoheptulose uptake by rat pancreatic islets or dispersed islet cells was found to represent a time-related and temperature-sensitive process inhibited by cytochalasin B. This mould metabolite also inhibited the efflux of D-[3H]-mannoheptulose from prelabelled islets.

Stimulus-secretion coupling of arginine-induced insulin release: comparison between the cationic amino acid and its methyl ester.

The role currently ascribed to the accumulation of L-arginine in the pancreatic islet B-cell as a determinant of its insulinotropic action was reevaluated by comparing the uptake and the metabolic, ionic, electric, and secretory effects of the cationic amino acid with those of its more positively charged methyl ester in rat pancreatic islets. The response to L-arginine methyl ester differed from that evoked by the unesterified amino acid by a lower uptake and oxidation, lack of inhibitory action on D-glucose metabolism, more severe inhibition of the catabolism of endogenous L-glutamine, inhibition of 45Ca net uptake, decrease in both 86Rb outflow from prelabeled islets perifused at normal extracellular Ca2+ concentration and 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+, and delayed and lesser insulinotropic action. These findings reinforce the view that the carrier-mediated entry of L-arginine into the islet B-cells, with resulting depolarization of the plasma membrane, represents the essential mechanism for stimulation of insulin release by this cationic amino acid.

Pancreatic fate of 14C-labelled hexoses.

In order to assess the respective contribution of the exocrine and endocrine moieties of the pancreas to the overall net uptake of selected monosaccharides by the pancreatic gland, the apparent distribution space of L-[1-14C]glucose, 3-O-[14C-methyl]-D-glucose, D-[U-14C]glucose, D-[U-14C]mannose and D-[U-14C]fructose was measured in pieces of pancreas obtained from either control rats or animals injected with streptozotocin. Although the time course for the uptake of 3-O-[14C-methyl]-D-glucose, D-[U-14C]glucose, D-[U-14C]mannose and D-[U-14C]fructose was much slower in the pieces of pancreas than that previously documented in isolated pancreatic islets, no significant difference could, as a rule, be detected between the results obtained in pancreatic pieces of control and streptozotocin rats. A comparable situation prevailed in the pancreas of animals examined 3 min after the intravenous injection of 3-O-[14C-methyl]-D-glucose.

Metabolism of alpha-D-[1,2-13C]glucose pentaacetate and alpha-D-glucose penta[2-13C]acetate in rat hepatocytes.

Hepatocytes from fed rats were incubated for 120 min in the presence of alpha-D-[1,2-13C]glucose pentaacetate (1.7 mM), both D-[1,2-13C]glucose (1.7 mM) and acetate (8.

Antitumoral action of 2-deoxy-D-glucose tetraacetate in human melanoma cells.

The ester 2-deoxy-D-glucose tetraacetate (2-DOGTA) was recently shown to display cytostatic and cytotoxic activity in various lines of tumoral cells. In the present work, it was found to inhibit cell growth and confer chemosensitivity to cisplatin in two lines of human melanoma cells, poorly responsive to cisplatin. The inhibition of cell growth by 2-DOGTA was apparently not attributable to alteration of either D-glucose utilization or oxidation in these melanoma cell lines.

Effects of D-mannoheptulose and its hexaacetate ester on hormonal secretion from the perfused pancreas.

D-mannoheptulose was recently proposed to be transported into cells by GLUT2, whereas its hexaacetate ester may cross the plasma membrane without requiring the intervention of a specific carrier system. In the light of these proposals, the effects of unesterified D-mannoheptulose and D-mannoheptulose hexaacetate upon hormonal secretion by the perfused rat pancreas were now investigated. Unesterified D-mannoheptulose (1.

Inhibitory action of the anomers of 2-deoxy-D-glucose tetraacetate on the metabolism of D-glucose in rat pancreatic islets.

Background: The tetra-acetate ester of 2-deoxy-D-glucose was recently found to either inhibit or augment insulin secretion, depending on the concentration of the ester. Both the positive and negative insulinotropic actions of the ester display anomeric specificity.

Methods: The effects of the alpha- and beta-anomer of 2-deoxy-D-glucose tetra-acetate (5.

Metabolism of D-[1,2-13C]glucose and alpha-D-[1,2-13C]glucose pentaacetate in tumoral pancreatic islet cells.

Tumoral pancreatic islet cells of the RINm5F line were incubated, in groups of 25x106 cells each, for 120 min at 37 degrees C in media (5. 0 ml) containing either alpha-D-[1,2-13C]glucose pentaacetate (1.7 mM) or both D-[1,2-13C]glucose (1.

Potentiation by 2-deoxy-D-glucose tetraacetate of the antitumoral action of 5-fluorouracil in mice inoculated with L1210 ascites-producing cells.

Ascites-producing tumoral cells of the L1210 line were inoculated to syngenic mice. The gain in body weight and survival time were measured in untreated animals and mice injected intraperitoneally 1, 5 and 9 days after the administration of the tumoral cells with 5-fluorouracil (20-200 microg/g body wt.) and/or 2-deoxy-D-glucose tetraacetate (75 or 1,350 microg/g body wt.

Differences in the time course of the metabolic response of B and non-B pancreatic islet cells to D-glucose and metabolized or non-metabolized hexose esters.

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Isomeric and anomeric specificity of the metabolic and secretory response of rat pancreatic islets to glucose pentaacetate.

In the presence of 2.8 mM D-glucose, beta-D-glucose pentaacetate (1. 7 mM) augmented insulin release from isolated rat pancreatic islets more than alpha-D-glucose pentaacetate.

Stimulation by 2-deoxy-D-glucose tetraacetates of hormonal secretion from the perfused rat pancreas.

The effects of alpha- and beta-2-deoxy-D-glucose tetraacetate (1.7 and 8.5 mM) on insulin, somatostatin, and glucagon secretion from isolated rat pancreases perfused in the presence of 8.

Opposite effects of D-glucose pentaacetate and D-galactose pentaacetate anomers on insulin release evoked by succinic acid dimethyl ester in rat pancreatic islets.

Both alpha- and beta-D-glucose pentaacetate (1.7 mM each) augmented, to almost the same extent, insulin release caused by succinic acid dimethyl ester (10.0 mM) in rat pancreatic islets.

Failure of streptozotocin tetraacetate to undergo extensive hydrolysis and to inhibit D-glucose metabolism and insulinotropic action in rat pancreatic islets.

The esterification of several monosaccharides, such as D-glucose, D-mannoheptulose and 2-deoxy-D-glucose was recently reported to increase their biological efficiency as either nutrient or antimetabolic agent. In the present study, however, the tetraacetate ester of streptozotocin was unexpectedly found to be less potent than unesterified streptozotocin in inhibiting D-glucose metabolism and insulinotropic action in isolated rat pancreatic islets. This coincided with a much lower rate for the hydrolysis of streptozotocin tetraacetate than D-glucose pentaacetate in islet homogenates.

Inhibition of insulin release by alpha- and beta-D-galactose pentaacetate.

Several monosaccharide polyacetate esters display higher biological efficiency than the corresponding unesterified carbohydrates, this being attributable to their capacity to cross the plasma membrane without requiring the intervention of a specific carrier system and to their subsequent intracellular esterase-catalyzed hydrolysis. Some of these esters, however, also exert a direct effect upon a receptor system apparently displaying analogies with that involved in the identification of bitter compounds by taste buds. For instance, under suitable experimental conditions, esters of non-nutrient monosaccharides, such as L-glucose, D-mannoheptulose or 2-deoxy-D-glucose, unexpectedly stimulate insulin release.

Insulinotropic action of the polyacetate esters of two non-nutrient monosaccharides in normal and diabetic rats.

The polyacetate esters of certain non-nutrient monosaccharides, such as L-glucose and 2-deoxy-D-glucose, were recently reported to display positive insulinotropic action and, hence, proposed as possible tools for stimulation of insulin release in non-insulin-dependent diabetes. In the present study, the secretory response to four carbohydrate esters was compared in islets of both normal and hereditary diabetic Goto-Kakizaki rats. Three major findings are documented.

Effects of D-mannoheptulose and its hexaacetate ester upon D-glucose metabolism in rat hepatocytes.

D-mannoheptulose, which inhibits hexokinase isoenzymes in a predominantly competitive manner, has been found to decrease much more modestly D-glucose metabolism in pancreatic islets exposed to a low, as distinct from high, concentration of the hexose. In the present study, which aimed at investigating the factor(s) possibly responsible for such a phenomenon, a comparable situation was found to prevail in rat hepatocytes. However, when the hexaacetate ester of D-mannoheptulose was used instead of the unesterified heptose, the relative extent of inhibition of D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to 14C-labelled acidic metabolites was comparable in hepatocytes exposed to either 1.

Insulinotropic action of beta-L-glucose pentaacetate.

The metabolism of beta-L-glucose pentaacetate and its interference with the catabolism of L-[U-14C]glutamine, [U-14C]palmitate, D-[U-14C]glucose, and D-[5-3H]glucose were examined in rat pancreatic islets. Likewise, attention was paid to the effects of this ester on the biosynthesis of islet peptides, the release of insulin from incubated or perifused islets, the functional behavior of individual B cells examined in a reverse hemolytic plaque assay of insulin secretion, adenylate cyclase activity in a membrane-enriched islet subcellular fraction, cAMP production by intact islets, tritiated inositol phosphate production by islets preincubated with myo-[2-3H]inositol, islet cell intracellular pH, 86Rb and 45Ca efflux from prelabeled perifused islets, and electrical activity in single isolated B cells. The results of these experiments were interpreted to indicate that the insulinotropic action of beta-L-glucose pentaacetate is not attributable to any nutritional value of the ester but, instead, appears to result from a direct effect of the ester itself on a yet unidentified receptor system, resulting in a decrease in K+ conductance, plasma membrane depolarization, and induction of electrical activity.

Effects of the polyacetate esters of nutrient and nonnutrient monosaccharides on 45calcium efflux and insulin release from perifused rat pancreatic islets.

Conclusion: The polyacetate esters of selected nonnutrient monosaccharides represent potential tools for either stimulation of insulin release in noninsulin-dependent diabetes or inhibition of insulin secretion in hyperinsulinemic syndromes.

Background: The polyacetate esters of several monosaccharides were recently shown to display greater nutritional value or biological efficiency than the corresponding unesterified carbohydrates.

Methods: The effects of seven polyacetate esters of monosaccharides, all tested at a 1.

Comparison of the effects of D-mannoheptulose and its hexaacetate ester on D-glucose metabolism and insulinotropic action in rat pancreatic islets.

It was recently, and surprisingly, found that D-mannoheptulose did not affect D-glucose metabolism and insulinotropic action in pancreatic islets incubated at a low concentration of D-glucose. To explain this finding, the metabolism and secretory response to the hexose were investigated in rat islets exposed to D-mannoheptulose hexaacetate, which was recently found to inhibit D-glucose catabolism in cells that are otherwise fully resistant to the heptose. At a high concentration of D-glucose (16.

Insulinotropic action of alpha-D-glucose pentaacetate: metabolic aspects.

The metabolism and metabolic effects of alpha-D-glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of alpha-D-glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of D-glucose in the islet cells.