W J Malaisse

..The meglitinide analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea glibenclamide of minimizing the risk of undesirable hypoglycemia...

....

..These findings are compatible with the view that selected (19)F-heptuloses may represent suitable tools for the non-invasive imaging of hepatocytes and insulin-producing cells by (19)F MRI...

..This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic metabolism...

..In particular, the metabolism and route of excretion of the drug allow its use in patients who have or may be at risk of diabetic nephropathy...

....

..These findings are interpreted as indicative of an impaired capacity of Ca2+ sequestration by intracellular organelles in the islet B-cells of thioacetamide-treated rats...

....

..These findings are consistent with the postulated enzyme-to-enzyme tunnelling of glycolytic intermediates between hexokinase isoenzyme(s), phosphoglucoisomerase and, possibly, phosphofructokinase...

..Thus, even over 60-min incubation at 30 degrees C, the integrated mean abundance of alpha- and beta-D-glucose would remain close to 82 and 89%, respectively, of the corresponding initial value (100%)...

....

..0 mM to 5.6 or 16.7 mM. These findings may suggest that the effect of D-glucose to increase the K+ content of islet cells represents one modality for coupling a rise in D-glucose concentration to stimulation of proinsulin biosynthesis...

..005). It is proposed that these findings indicate isotopic discrimination at the phosphoglucoisomerase level between (12)C and (13)C for the carbon atom in position 1 (as compared to that in position 2) of D-fructose 6-phosphate...

..It is proposed that the anomeric specificity of D-glucose metabolism is essential to a sound understanding of carbohydrate homeostasis in health and disease...

....

....

..In all these cases, the findings in rats fed a diabetes-promoting diet are compared to those collected in animals receiving a protective diabetes-retardant diet...

..Moreover, the results suggest that to oppose such consequences, e.g. liver steatosis, it may be necessary to combine the dietary supply of omega3 acids with a suitable control of food intake, in both qualitative and quantitative terms...

..Attention is also drawn to the latest approaches for noninvasive imaging and functional characterization of pancreatic beta cells. None of these procedures is used in clinical practice yet...

....

..Emphasis is placed, therefore, on the unusual situation found in the soleus muscle of omega3-depleted rats, in which both lipid and metabolic variables may be either favourably or adversely affected by the same environmental factor(s)...

....

....

..In the light of results obtained with 6-deoxy-6-iodo-D-glucose, it is proposed that 7-deoxy-7-iodo-D-mannoheptulose could be used for the non-invasive imaging of the endocrine pancreas...

....

....

..These contrasting findings may be relevant to the higher coronary heart disease risk prevailing in female, as compared to male, diabetic subjects...

....

..The present procedure may thus allow the assessment of the relative contribution of islet beta-cells to the total mass of the pancreatic gland...

..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...

....

....

....

....

....

..These findings provide further support to the validity of D-[3H]mannoheptulose uptake as a tool to assess the density of insulin-producing cells in isolated islets...

..These findings are compatible with the hypothesis that D-mannoheptulose is transported into cells mainly, if not exclusively, at the intervention of GLUT2...

..It is proposed that selected esters of saccharides represent useful tools to bypass defects in hexose transport, and to increase their nutritional or therapeutic efficiency...

..These findings indicate that the cationic events coupling the recognition of D-glucose to the stimulation of insulin release are not identical in islets exposed to the hexose or its ester...

....

..relative values (by reference to the phosphorylation rate of 10 mM D-glucose), and sensitivity to inhibition by D-glucose (10 mM)...

..The ester of D-mannoheptulose could thus represent a useful tool to inhibit hexose phosphorylation and interfere with cell growth in cells otherwise resistant to the heptose...

..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...

..These findings suggest that factors such as the intracellular transport and availability of the heptose may interfere with the expression of its antagonistic action upon D-glucose metabolism...

..These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids...

..It is concluded, therefore, that neither D-mannoheptose nor D-glycero-D-guloheptose can be considered as suitable substitutes of D-mannoheptulose...

....

..Suitably radiolabelled D-mannoheptulose or an analogue of the heptose could thus conceivably be used for quantification of the endocrine pancreatic mass...

..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...

....

..Our data show a reduced expression of AQP7 at the protein level in adipose tissue from n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-(14)C]-Glycerol uptake was not modified in adipocytes from n3-PUFA-depleted animals...

..These findings suggest that an insufficient uptake of the heptose accounts, in part at least, for its poor efficiency as inhibitor of D-glucose catabolism in liver, and presumably islet cells exposed to low concentrations of the hexose...

....

..It is concluded that the intrinsic catalytic properties of B-cell glucokinase cannot fully account for the concentration dependency and sugar specificity of the secretory response to D-glucose or other hexoses in pancreatic islets...

..These findings thus argue against a low expression of either low-Km hexokinase(s) or lactate dehydrogenase as major determinants of the glucose-sensing device in beta-cells...

....

..0 mM). These findings indicate that the present approach indeed allows to assess the relative contribution of B-cells to total islet mass for purpose of comparison between animals with different metabolic and/or hormonal status...

..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...

....

..These findings support the view that the entry of D-mannoheptulose into cells may be mediated by a cytochalasin B-sensitive transport system, such as the GLUT2 carrier...

..It is concluded, therefore, that the mechanism of action of formycin A in the pancreatic beta-cell remains to be elucidated...

..This study thus reveals that formycin A may display cytotoxic potential in the same range of concentrations in which it causes a progressive increase of glucose-stimulated insulin secretion in normal pancreatic islets...

....

..It is proposed that suitably radiolabelled D-mannoheptulose could be used to label preferentially the endocrine moiety of the pancreatic gland, e.g., in the perspective of its non-invasive imaging...

....

..This study thus emphasizes the vastly different pharmacodynamics of nateglinide and glibenclamide in both control and diabetic rats...

..In light of these and previous findings, it is proposed that the beneficial metabolic and functional events of the MCT:FO emulsion may display not solely a rapid but also sustained time course...

....

....

..These findings may help to define the experimental conditions optimal for the labeling and accumulation of islet glycogen in vivo...

..This topic was first reviewed in 1998 (2). The major aim of the present report is to briefly evoke the background and present knowledge in this field...

....

..Thus, lipid peroxidation in key organs is not necessarily related to the development of metabolic disorders associated with diabetes and obesity...

....

....

..g. by 11C-labelled D-glucose or 2-deoxy-2-[18F]fluoro-D-glucose, may allow identification and localization of insulinomas in the pancreatic gland by a non-invasive imaging procedure...

..However, the supply of exogenous omega3 fatty acids to the omega3-depleted rats failed to oppose visceral obesity, possibly as a result of the orexigenic effects of these omega3 fatty acids...

..It could be attributable, in part at least, to D-glucose and D-mannoheptulose countertransport, resulting inter alia in a greater net uptake of the heptose by B cells exposed to a high concentration of the hexose...

..The cationic alterations were corrected, in part at least, by the prior intravenous injection of the medium-chain triglyceride:fish oil emulsion 60 min before sacrifice of the omega3-depleted rats...

..Moreover, in the uninjected omega3-depleted rats the comparison between individual plasma and liver measurements indicated positive correlations in the fatty acid profile of phospholipids and triglycerides...

..However, the possible role of Na(+) co-transport in the secretory response to L-alanine cannot be ignored...

..In conclusion, an impaired activity of the Na,K-ATPase in insulin-producing cells apparently represents a key determinant of altered islet function in omega3-depleted rats...

..8 mM, rather than 8.3 mM D-glucose. These findings suggest, therefore, that the postulated process of enzyme-to-enzyme channelling involves mainly glucokinase...

....

....

..These results suggest that methyl pyruvate could be used as an insulinotropic agent to bypass site-specific defects of D-glucose metabolism in the B-cell, such as those found in starvation or non-insulin-dependent diabetes mellitus...

....

..80 mM) and then further cultured for 64 h in the absence of the ester. These findings indicate that such an ester acts as a powerful cytostatic and cytotoxic agent in this tumoral cell line...

..However, the mechanism of this resistance is still not explained...

..The latter two conditions may be operative in islets exposed to a high concentration of D-glucose, this accounting for the exquisite sensitivity to D-mannoheptulose of glucose-stimulated islets...

..It is speculated that these findings may extend to insulin-producing cells, the knowledge that aliphatic dioic acids or their esters may act as energy substrates, e.g. in parenteral nutrition...

..g. hepatocytes and pancreatic islet cells, in which no oscillation of glycolysis was so far observed...

....

..These findings indicate that a suitable radioactive analog of D-mannoheptulose could be used, in human like in rat islets, for preferential labelling of the endocrine moiety of the pancreatic gland...

..It is proposed, therefore, that 11C-labelled D-glucose, rather than 2-deoxy-2-[18F]fluoro-D-glucose should be used in the perspective of the non-invasive imaging of the endocrine pancreas...

..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...

..Nevertheless, under suitable experimental conditions, 6-O-octanoyl-D-glucose and 6-O-decanoyl-D-glucose significantly augmented insulin output, suggesting that such esters could be used, instead of D-glucose itself, as cell nutrients...

..Its potential use for gene therapy is also considered, therefore, in this report...