Disease relevance of NSC1217

• Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin [1].

High impact information on NSC1217

• The use of radiolabelled analogs of D-mannoheptulose suitable for imaging of the endocrine pancreas is discussed [2].
• 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 [2].
• Potential techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or d-mannoheptulose [3].
• Its uptake coincides with the intracellular accumulation of acidic metabolites generated by phosphorylation of D-mannoheptulose [4].
• These metabolites remain in the islet cells after prolonged washing, suggesting that imaging of the pancreas at a relatively late time after intravenous administration of D-mannoheptulose could avoid significant extracellular contamination [4].

Biological context of NSC1217

• Behavioral and metabolic effects of intraperitoneal D-mannoheptulose (MH) injections were investigated in rats fed a high carbohydrate (HC) or a high fat (HF) diet [5].
• Changes in food intake and meal patterns following injection of D-mannoheptulose in rats [5].
• A narrow substrate specificity; high Km values for the two substrates, D-glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody [6].

Anatomical context of NSC1217

• Effects of D-mannoheptulose and its hexaacetate ester on hormonal secretion from the perfused pancreas [7].
• Likewise, a preferential labelling of hepatocytes and insulin-producing transplanted cells can be achieved in vivo after administration of tritiated D-mannoheptulose [4].
• Uptake of D-mannoheptulose by rat erythrocytes, hepatocytes and parotid cells [8].
• A comparable metabolic response to D-mannoheptulose is indeed observed in purified B cells [9].
• The modality by which D-mannoheptulose apparently gains access to the cytosol of these cells remains to be elucidated [7].

Associations of NSC1217 with other chemical compounds

• The experimental data revealed a mixed type of D-mannoheptulose inhibitory action upon D-glucose phosphorylation, predominantly of the non-competitive and competitive type, in liver and parotid homogenates, respectively [10].
• Tritiated D-mannoheptulose, a ketoheptose known to inhibit D-glucose metabolism in hepatocytes and pancreatic islets, but not so in pancreatic acinar cells, was injected intravenously in streptozotocin-induced diabetic mice transplanted under the kidney capsule with islets from control mice of the same strain [11].
• 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) [12].
• It is proposed, therefore, that D-mannoheptulose hexaacetate crosses efficiently the plasma membrane of parotid cells and, after intracellular hydrolysis, allows inhibition of D-glucose phosphorylation by the unesterified heptose [13].

Gene context of NSC1217

• D-mannoheptulose phosphorylation by hexokinase isoenzymes [14].
• Since GLUT1, rather than GLUT2, represents the major carrier system for the transport of monosaccharides across the islet B-cell plasma membrane in human subjects, the uptake of D-mannoheptulose and its metabolic and secretory effects were investigated in human islets [15].
• These findings thus document anomeric specificity in terms of the inhibitory action of D-mannoheptulose upon alpha- versus beta-D-glucose phosphorylation by either hexokinase or glucokinase [16].
• Unesterified D-mannoheptulose (1.7 mM) inhibited insulin release and, in most cases, somatostatin output, whereas it augmented glucagon secretion by pancreases exposed to D-glucose (3.3 mM) in the presence of the dimethyl ester of succinic acid (SAD, 10.0 mM) [7].

References