ASSESSING THE FORAGING BEHAVIOR OF AGRIOTES SORDIDUS WIREWORMS IN DUAL-CHOICE OLFACTOMETERS.

The different steps of the foraging process of wireworms (Coleoptera: Elateridae) would be better understood if accurate and holistic information regarding the role of plant-produced chemicals constituting their environment were available. Volatile organic compounds (VOC) play important roles in the interactions between plants and insects in many ecosystems, whether they take place aboveground or below-ground. The roles of VOC are still relatively unknown for wireworms, and deserve attention. Here, we performed three experimentations with barley roots as baits. In the two first, we assessed the effect of chopped roots and fungus infected roots on the orientation of wireworms. In the third experiment, the larvae were confronted to both healthy and fungus infected roots. We discuss the results in terms of suitability of the olfactometers we designed for the investigation of olfaction in wireworms, and we provide suggestions to improve their use.

Development of a colorimetric method for the dosage of OI- anions and I2 in aqueous media.

Lactoperoxidase catalyzes the oxidation of thiocyanate (SCN-) and iodide (I-) in presence of hydrogen peroxide in hypothiocyanite (OSCN-) ions and, depending on the pH, in hypoiodite (OI-) ions or in iode (I2). Oxidized SCN- and I- are part of the lactoperoxidase system, which is a natural biological protection in cow milk, and are described as having inhibitory properties against pathogenic human bacteria, fungi and viruses. We have developed an aqueous solution containing only OSCN- and OI- ions (without the enzyme) and we tested it successfully against plant pathogens. In order to characterize this new soft chemical control against plant pathogens we had to determine the concentration of OSCN- and OI- ions. The dosage of OSCN- consists in a well referenced colorimetric method but no procedure is described for the determination of OI- ions. We have thus developed an easy method, based on the oxidation of the amine moiety of 3,3',5,5'- tetramethylbenzidine (TMB) by OI- or I2 in a strongly absorbing blue product for the detection and dosage of both molecules. Interestingly the OSCN- ions are not able to oxidize TMB and render this method specific to enzymatic oxidized iodide. We have calculated its sensitivity, repeatability and linearity. This method could also be used for the determination of OCI- and OBr- ions produced during the enzymatic oxidation of chloride and bromide by mammalian's peroxidases.

Biological control of grey mould in strawberry fruits by halophilic bacteria.

AIMS: Grey mould caused by Botrytis cinerea is an economically important disease of strawberries in Tunisia and worldwide. The aim of this study was to select effective halophilic bacteria from hypersaline ecosystems and evaluate the abilities of antifungal bacteria to secrete extracellular hydrolytic enzymes, anti-Botrytis metabolites and volatiles. METHODS AND RESULTS: Grey mould was reduced in strawberry fruits treated with halophilic antagonists and artificially inoculated with B. cinerea. Thirty strains (20.2%) were active against the pathogen and reduced the percentage of fruits infected after 3 days of storage at 20 degrees C, from 50% to 91.66%. The antagonists were characterized by phenotypic tests and 16S rDNA sequencing. They were identified as belonging to one of the species: Virgibacillus marismortui, B. subtilis, B. pumilus, B. licheniformis, Terribacillus halophilus, Halomonas elongata, Planococcus rifietoensis, Staphylococcus equorum and Staphylococcus sp. The effective isolates were tested for antifungal secondary metabolites. CONCLUSIONS: Moderately halophilic bacteria may be useful in biological control against this pathogen during postharvest storage of strawberries. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of such bacteria may constitute an important alternative to synthetic fungicides. These moderate halophiles can be exploited in commercial production and application of the effective strains under storage and greenhouse conditions.

Enzyme-to-enzyme channelling in the early steps of glycolysis in rat pancreatic islets.

The metabolism of D-glucose displays anomeric specificity in rat pancreatic islets. The aim of the present report is to investigate whether such a situation implies enzyme-to-enzyme tunnelling of metabolites in the early steps of glycolysis. For such a purpose, the modelling of alpha- and beta-D-glucose catabolism, itself based on available information concerning both the utilisation of these two anomers and the intrinsic properties of phosphoglucoisomerase, was first examined. According to a theoretical model with enzyme-to-enzyme channelling, the generation of 3HOH from D-[2-3H]glucose should be higher in islets exposed to beta-D-glucose rather than alpha-D-glucose, whilst the opposite situation should prevail in the case of D-[5-3H]glucose conversion to 3HOH. Experimental data collected in rat islets incubated for 60 min at 4 degrees C in the presence of either alpha- or beta-D-glucose mixed with tracer amounts of either alpha- or beta-D-[2- 3H]glucose and alpha- or beta-D-[5-3H]glucose indicate that the beta/alpha ratio for D-[2-3H]glucose conversion to 3HOH is indeed higher than the beta/alpha ratio for D-[5-3H]glucose conversion to 3HOH. These findings are consistent with the postulated enzyme-to-enzyme tunnelling of glycolytic intermediates between hexokinase isoenzyme(s), phosphoglucoisomerase and, possibly, phosphofructokinase.

Metabolism of tritiated D-glucose anomers in rat erythrocytes.

It was recently proposed that alpha-D-glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-glucose but not significantly different from unity in the presence of beta-D-glucose. These findings emphasize the relevance of alpha-D-glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-glucose in distinct cell types.

Metabolism of D-glucose anomers in rat pancreatic islets exposed to equilibrated D-glucose.

This study aims at establishing the contribution of alpha- and beta-D-glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-glucose at anomeric equilibrium, the metabolic fate of alpha-D-glucose differs vastly from that of beta-D-glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-glucose 6-phosphate.

Labelling of lipids by D-[1-14C]glucose, D-[6-14C] glucose and D-[3-3H]glucose in pancreatic islets from normal and GK rats.

In pancreatic islets prepared from either normal or GK rats and incubated at either low (2.8 mM) or high (16.7 mM) D-glucose concentration, the labelling of both lipids and their glycerol moiety is higher in the presence of D-[1-14C]glucose than D-[6-14C]glucose. The rise in D-glucose concentration augments the labelling of lipids, the paired 14C/3H ratio found in islets exposed to both D-[1-14C]glucose or D-[6-14C]glucose and D-[3-3H]glucose being even slightly higher at 16.7 mM D-glucose than that found, under otherwise identical conditions, at 2.8 mM D-glucose. Such a paired ratio exceeds unity in islets exposed to D-[1-14C]glucose. The labelling of islet lipids by D-[6-14C]glucose is about 30 times lower than the generation of acidic metabolites from the same tracer. These findings indicate (i) that the labelling of islet lipids accounts for only a minor fraction of D-glucose catabolism in pancreatic islets, (ii) a greater escape to L-glycerol-3-phosphate of glycerone-3-phosphate generated from the C1-C2-C3 moiety of D-glucose than D-glyceraldehyde-3-phosphate produced from the C4-C5-C6 moiety of the hexose, (iii) that only a limited amount of [3-3H]glycerone 3-phosphate generated from D-[3-3H]glucose is detritiated at the triose phosphate isomerase level before being converted to L-glycerol-3-phosphate, and (iv) that a rise in D-glucose concentration results in an increased labelling of islet lipids, this phenomenon being somewhat more pronounced in the case of D-[1-14C]glucose or D-[6-14C]glucose rather than D-[3-3H]glucose.

Metabolic interactions between D-glucose and D-fructose in pancreatic islets

No disponible

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. After 60 min incubation at 37 degrees C, the apparent intracellular distribution space of the tritiated heptose was close to or somewhat higher than that of D-[5-3H]glucose and close to 50% of the intracellular 3HOH space. It was further enhanced by D-glucose and a high concentration of 10 mM of D-mannoheptulose. The uptake of D-[3H]mannoheptulose was much lower however than that of D-[3H]mannoheptulose hexaacetate. As judged from the fate of D-mannoheptulose hexa[2-14C]acetate, the latter ester was efficiently hydrolyzed in the islet cells. The internalization of D-[3H]mannoheptulose (or its ester) coincided with the generation of tritiated acidic metabolites, reflecting phosphorylation of the heptose. The situation found in normal islet cells sharply differed from that found in tumoral islet cells of either the RINm5F or INS-1 line, in which the apparent distribution space of D-[3H]mannoheptulose represented only about 3 and 9%, respectively, of the intracellular 3HOH space. These results indicate that the entry of D-mannoheptulose into islet cells represents a carrier-mediated process, possibly mediated at the intervention of GLUT2 and, hence, provide further support to the possible use of a suitable D-mannoheptulose analog as a tool for the preferential labelling of insulin-producing cells in the pancreatic gland.

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

Cationic determinants of D-fructose insulinotropic action.

In the absence of any other exogenous nutrient, D-fructose stimulates insulin release from rat pancreatic islets provided that it is tested at high concentrations in excess of a threshold value close to 80 mM, an optimal secretory response being recorded at 240 mM. In the present study, the cationic determinants of the insulinotropic action of D-fructose, used at the latter high concentration, were explored in perifused rat islets that had been prelabelled with either 86Rb or 45Ca. The changes in 86Rb outflow and 45Ca efflux evoked by 240 mM D-fructose were comparable to those caused by 11.1 mM D-glucose in that both hexoses inhibited 86Rb and 45Ca outflow and, at normal Ca2+ concentration, caused a secondary rise in 45Ca efflux. These cationic changes coincided with stimulation of insulin release. The major differences between the two series of experiments consisted, in the islets exposed to D-fructose, in the occurrence of an early and transient increase in 45Ca efflux at normal extracellular Ca2+ concentration, a secondary reascension in 86Rb outflow and a dramatic off-response in both 86Rb and 45Ca outflow as well as insulin release. These phenomena were also observed in islets exposed to 240 mM 3-O-methyl-D-glucose, suggesting that they may be linked to the massive influx (or efflux) of monosaccharides, as possibly accompanied by Na+ inward co-transport, mobilization of Ca2+ from intracellular stores and activation of voltage- and/or Ca(2+)-sensitive K+ channels. This interpretation was supported by the finding that, at high concentrations (80.0 mM) of D-glucose or D-mannose, the aldohexoses also provoked a reascension in 86Rb outflow and off-response in insulin release. The cationic determinants of the insulinotropic action of D-fructose, in high concentration (240 mM), thus appear similar, if not identical, to those currently incriminated in the stimulation of insulin release by D-glucose.

Possible role of diadenosine polyphosphates in glucose-stimulated insulin release: effects of NaF upon metabolic and functional variables in rat isolated islets.

Diadenosine polyphosphates, such as diadenosine triphosphate (A2P3) and diadenosine tetraphosphate (A2P4), were recently proposed to participate in the stimulus-secretion coupling for nutrient-stimulated insulin release. Since NaF, an inhibitor of inorganic pyrophosphatase, was reported to lower A2P3 and A2P4 content in glucose-stimulated pancreatic islets, its effects upon metabolic, cationic, biosynthetic and secretory variables in rat pancreatic islets were investigated in the present study. Up to a concentration close to 0.1 mM, NaF failed to affect most of these variables, except for a decrease in 45Ca net uptake. Much higher concentrations of NaF (e.g. 5.0 mM) were required to cause inhibition of the metabolic, ionic, biosynthetic and secretory responses of the islets to nutrient secretagogues. Yet, even at this high concentration, NaF failed to lower the islet content in tritiated A2P3 and A2P4 in islets prelabelled with [2,8-3H]adenosine and failed to prevent the glucose-induced increase in such a content. It is concluded, therefore, that NaF may not represent a suitable tool to assess the participation of diadenosine polyphosphates in the process of nutrient-induced insulin secretion.

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.

Effect of D-mannoheptulose upon the cationic and secretory responses to alpha-D-glucose pentaacetate in perifused rat pancreatic islets.

The metabolism of alpha-D-glucose pentaacetate and its positive insulinotropic action in isolated rat pancreatic islets are both unexpectedly resistant to D-mannoheptulose, as judged from experiments conducted over 90-120 min incubation. In the present study, the possible effects of the heptose upon the immediate cationic and secretory response to the ester were investigated in perifused islets prelabeled with either 86Rb or 45Ca. At a 10 mM concentration, sufficient to abolish the inhibitory action of unesterified D-glucose upon 86Rb outflow, D-mannoheptulose failed to suppress the decrease in 86Rb outflow and increase in 45Ca efflux caused by alpha-D-glucose pentaacetate at normal extracellular Ca2+ concentration and also failed to prevent the decrease in both 45Ca and insulin release provoked by the ester in the absence of extracellular Ca2+. The sole obvious effect of the heptose was to change the early peak-shaped positive secretory response to alpha-D-glucose pentaacetate to a transient inhibition of insulin release. This change was observed in islets either deprived of any other exogenous nutrient or exposed to L-leucine throughout the experiments. These findings support the view that the islet functional response to alpha-D-glucose pentaacetate is largely resistant to D-mannoheptulose. They also reinforce the concept that the insulinotropic action of this and other monosaccharide esters involves a dual modality of B-cell activation, linked to both the catabolism of their carbohydrate moieties and a direct effect of the esters themselves upon a specific receptor system.

Effect of the meglitinide analog S21403 on cationic fluxes and insulin release in perifused rat pancreatic islets exposed to a high concentration of D-glucose.

The effect of the meglitinide analog S21403 (10 microm) upon(86)Rb and(45)Ca outflow and insulin release was investigated in perifused rat islets exposed to a high concentration of D-glucose (16.7 mm) in order to simulate the situation found in diabetic patients. Under these conditions, S21403 provoked a rapid, sustained and rapidly reversible increase in(86)Rb outflow, (45)Ca efflux and insulin release. These effects were suppressed or reversed when the experiments were conducted in the absence of extracellular Ca2+. They support the view that S21043 could be used as a novel insulinotropic tool in the treatment of non-insulin-dependent diabetes mellitus, the cationic and secretory responses to the drug displaying a favourable time course for prompt and not unduly prolonged activation of islet B-cells.

Inhibition of glucose-induced insulin release by 3-O-methyl-D-glucose: enzymatic, metabolic and cationic determinants.

The analog of D-glucose, 3-O-methyl-D-glucose, is thought to delay the equilibration of D-glucose concentration across the plasma membrane of pancreatic islet B-cells, but not to exert any marked inhibitory action upon the late phase of glucose-stimulated insulin release. In this study, however, 3-O-methyl-D-glucose, when tested in high concentrations (30-80 mM) was found to cause a rapid, sustained and not rapidly reversible inhibition of glucose-induced insulin release in rat pancreatic islets. In relative terms, the inhibitory action of 3-O-methyl-D-glucose was more marked at low than high concentrations of D-glucose. It could not be attributed to hyperosmolarity and appeared specific for the insulinotropic action of D-glucose, as distinct from non-glucidic nutrient secretagogues. Although 3-O-methyl-D-glucose and D-glucose failed to exert any reciprocal effect upon the steady-state value for the net uptake of these monosaccharides by the islets, the glucose analog inhibited D-[5-3H]glucose utilization and D-[U-14C]glucose oxidation. This coincided with increased 86Rb outflow and decreased 45Ca outflow from prelabelled islets, as well as decreased 45Ca net uptake. A preferential effect of 3-O-methyl-D-glucose upon the first phase of glucose-stimulated insulin release was judged compatible with an altered initial rate of D-glucose entry into islet B-cells. The long-term inhibitory action of the glucose analog upon the metabolic and secretory response to D-glucose, however, may be due, in part at least, to an impaired rate of D-glucose phosphorylation. The phosphorylation of the hexose by beef heart hexokinase and human B-cell glucokinase, as well as by parotid and islet homogenates, was indeed inhibited by 3-O-methyl-D-glucose. The relationship between insulin release and D-glucose utilization or oxidation in the presence of 3-O-methyl-D-glucose was not different from that otherwise observed at increasing concentrations of either D-glucose or D-mannoheptulose. It is concluded, therefore, that 3-O-methyl-D-glucose adversely affects the metabolism and insulinotropic action of D-glucose by a mechanism largely unrelated to changes in the intracellular concentration of the latter hexose.

Effects of alpha-D- and beta-L-glucose pentaacetate on effluent radioactivity from pancreatic islets labelled with [(32)P]phosphate and myo-[2-(3)H]inositol.

The anomers of both D-glucose pentaacetate and L-glucose pentaacetate were recently found to display insulinotropic potential. In order to progress in understanding the mode of action of these esters in islet cells, we have now investigated whether they mimic the effect of nutrient secretagogues to cause a phosphate flush and activation of phospholipase C in isolated islets. For this purpose, rat pancreatic islets were prelabelled with either [(32)P]orthophosphate or myo-[2-(3)H]inositol and placed in a perifusion chamber. In the absence of any other exogenous nutrient, the administration of alpha-D-glucose pentaacetate (1.7 mM) from 46 to 70 min of perifusion increased, after an initial transient fall, both 32P and 3H fractional outflow rates and stimulated insulin release from the perifused islets. No secondary rise in either (32)P or (3)H outflow and no sizeable stimulation of insulin release was observed, however, in response to Beta-L-glucose pentaacetate (also 1.7 mM). These findings are consistent with the view that the insulinotropic action of alpha-D-glucose pentaacetate entails a nutrient-like component leading to the occurrence of both a phosphate flush and hydrolysis of phosphoinositides. This is not the case, however, for Beta-L-glucose pentaacetate. The latter ester might act directly on a yet unidentified receptor, the early secretory response to alpha-D-glucose pentaacetate also apparently involving such a direct effect of the ester itself.

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.

99mTc-sesta-(2-methoxy-isobutyl-isonitrile) uptake by pancreatic islets, parotid cells, and mammary carcinoma cells.

99mTc-sesta-(2-methoxy-isobutyl-isonitrile)(Tc-MIBI) is currently used for imaging of several organs. In the present study, its uptake by rat pancreatic islets, rat parotid cells, and human breast adenocarcinoma cells (MCF-7 cells) was found to be grossly proportional to its concentration (up to 0.1 microM), time-related (with a fractional turnover rate close to 2-3 10(-2).min(-1)), and stimulated by D-glucose. Comparable values for the fractional turnover rate were found in prelabeled islets and MCF-7 cells, D-glucose failing to affect Tc-MIBI efflux from prelabeled islets. In the islets, the uptake of Tc-MIBI was decreased at low temperature, in the presence of mitochondrial poisons and at high extracellular K+ concentration, unaffected by the absence of extracellular Ca2+, and increased by nutrient secretagogs, such as 2-ketoisocaproate and the association of L-leucine and L-glutamine. These findings are consistent with the view that Tc-MIBI uptake is ruled by its extracellular concentration, and the polarization of both plasma and mitochondrial membranes. It is proposed that this lipophilic cation may be useful to detect alteration of nutrient metabolism in pancreatic islets deprived of any exogenous fuel.

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 1.7-mM concentration, on both 45Ca efflux and insulin release were investigated in prelabeled rat pancreatic islets perifused in the presence of 10.0 mM succinic acid dimethyl ester. RESULTS: Both alpha-D-glucose penta-acetate and, to a lesser extent, beta-L-glucose penta-acetate stimulated insulin release. Inversely, alpha-D-galactose penta-acetate, but not beta-D-galactose penta-acetate inhibited insulin secretion evoked by succinic acid dimethyl ester. Esters of carbohydrates which are inhibitors of D-glucose metabolism, such as D-mannoheptulose hexa-acetate and the two anomers of 2-deoxy-D-glucose tetra-acetate also enhanced insulin output, with a preference for the alpha-anomer of 2-deoxy-D-glucose tetra-acetate. Only those esters with positive insulinotropic action augmented 45Ca efflux from the prelabeled islets.