Disease relevance of MANNOHEPTULOSE

• The potential of the naturally occurring sugar, mannoheptulose (which is purified from avocados and is assumed to be of low toxicity), as a cancer treatment is discussed [1].
• After acute pancreatectomy (P) or mannoheptulose treatment [0.14 mmole per 100 gm body weight (Group M)], similar cholestatic effects were observed (-0.29 and -0.27 microliter per min per gm liver, respectively) [2].
• Since administration of mannoheptulose induces temporary hyperglycemia, the present study was conducted to elucidate this phenomenon [3].
• The presence of defective regulation of the glycolytic pathway by mannoheptulose in suckling and weanling rats may contribute to development of hyperinsulinemia in fa/fa rats [4].
• Administration of mannoheptulose partially protected mice infected with Listeria monocytogenes against the lethal effect of a subsequent endotoxin challenge [5].

High impact information on MANNOHEPTULOSE

• Because mannoheptulose, a specific HK inhibitor, blocks the severe repression triggered by 2-deoxyglucose and yet the phosphorylated products per se do not act as repression signals, we propose that HK may have dual functions and may act as a key sensor and signal transmitter of sugar repression in higher plants [6].
• High Km glucose-phosphorylating (glucokinase) activities in a range of tumor cell lines and inhibition of rates of tumor growth by the specific enzyme inhibitor mannoheptulose [1].
• Rates of growth of human tumors in experimental animals are dramatically reduced (by 65-79%) by a dose of 1.7 mg/g mannoheptulose daily for 5 days [1].
• GKA1 increased the affinity of GK for the competitive inhibitor mannoheptulose but did not affect the affinity for the inhibitors palmitoyl-CoA and the endogenous 68-kDa regulator (GK regulatory protein [GKRP]), which bind to allosteric sites or to N-acetylglucosamine, which binds to the catalytic site [7].
• This effect of glucose was counteracted by competitive inhibitors of glucokinase (5-thioglucose and mannoheptulose) but was unaffected by fructose analogs and may be due to changes in cell shape or conformation of the cytoskeleton that are secondary to glucose metabolism [8].

Biological context of MANNOHEPTULOSE

• Ten millimolar mannoheptulose, which inhibits phosphorylation of glucose and blocks glucose-stimulated insulin release, had little effect on the stimulation of insulin release by 0.3 mM 59-801 from islets incubated with 3 mM glucose [9].
• Glycolysis inhibitor mannoheptulose suppressed the stimulatory effect of 16.7 mM glucose on GLUT2 mRNA and protein [10].
• The anomalous effects of mannoheptulose on glucokinase translocation and on the kinetics of purified glucokinase could be explained by a second glucose-binding site on glucokinase [11].
• Incubation of INS-1 cells with 30mM mannoheptulose, an inhibitor of glucose metabolism, blunted all glucose-induced gene expression but left the 3-MG effects unaltered [12].
• We investigated the kinetics of the mitochondrial respiratory chain, proton leak, and phosphorylating subsystems of liver mitochondria from mannoheptulose-treated and control rats [13].

Anatomical context of MANNOHEPTULOSE

• The incorporation of [14C]choline into PC of isolated pancreatic islets of the rat was time dependent, glucose stimulable, and inhibited by mannoheptulose [14].
• In contrast, mannoheptulose (5 mM) did not affect D-, A-, or B-cell responses to glyceraldehyde (5 mM) in the absence of glucose [15].
• To investigate how the D-cell recognizes the glucose stimulus, the hormone response to (1) glucose, (2) the trioses glyceraldehyde and dihydroxyacetone, (3) the metabolic blocker, mannoheptulose, and (4) the low- or nonmetabolized sugars galactose, fructose, or ribose were studied using the isolated dog pancreas [15].
• 3-O-Methyl-D-Glc, which cannot be phosphorylated, and Glc plus mannoheptulose induced a decrease of transport activity caused by the reduction of VvHT1 protein in the plasma membrane without affecting VvHT1 transcript levels [16].
• Insulin deficiency induced with mannoheptulose inhibited the restoration of 14C-lipid accumulation in white adipose tissue on refeeding of lactating rats with pups removed, but did not prevent the restoration of 14C-lipid accumulation in mammary gland [17].

Associations of MANNOHEPTULOSE with other chemical compounds

• The effect of glucose was blocked by the glucokinase inhibitors mannoheptulose and glucosamine and was not mimicked by the 3-O-methyl or 6-deoxy analogues of glucose, which are not phosphorylated [18].
• The potency, dependency on glucose concentration, lack of inhibition by mannoheptulose, and lack of effect on glycolysis of 59-801 were similar to that of tolbutamide [9].
• The glucokinase inhibitor mannoheptulose (20 mM) had no adverse effect on the secretory response to 20 mM methyl pyruvate, whereas 10 microM forskolin amplified the insulinotropic action of MP [19].
• By contrast, D-mannoheptulose reduced only marginally the islet metabolism at 3 mmol/l glucose, which is consistent with an effective mannoheptulose-induced inhibition of the glucokinase-dependent, minor part of glucose phosphorylation at this low glucose concentration [20].
• The effect of glucose was abolished by the KATP-channel opener diazoxide as well as by mannoheptulose and azide, inhibitors of glycolysis and mitochondrial metabolism [21].

Gene context of MANNOHEPTULOSE

• (3) Mannoheptulose (5 mM) attenuated somatostatin and insulin secretion to 8.3 mM glucose, while it augmented glucagon output [15].
• Furthermore, we show that mannoheptulose, a specific HXK inhibitor, restores germination of seeds grown in the presence of Man. We conclude that HXK is involved in the Man-mediated repression of germination of Arabidopsis seeds, possibly via energy depletion [22].
• 4. Intramitochondrial succinyl-CoA content was lower in whole liver homogenates and in mitochondria isolated from animals treated with glucagon or mannoheptulose [23].
• The glucokinase inhibitor mannoheptulose (20 mM) had no effect on its secretory action, while the protein kinase-C inhibitor staurosporine (20 nM) reduced secretion to MMSucc [24].
• 6) These inhibitory effects of IL-1 were abolished if mannoheptulose was included during the 2-h incubation with 7 mM glucose plus 5.0 nM IL-1 [25].

Analytical, diagnostic and therapeutic context of MANNOHEPTULOSE

• Low (30%) or no ADP and mannoheptulose inhibition is observed with hexokinase and fructokinase activities derived from the cytosolic compartment obtained after ion exchange and affinity chromatography [26].
• Intraperitoneal injection of 2 ml of a 30% solution of mannoheptulose, an inhibitor of islet glucose metabolism, decreased the serum insulin concentrations although the serum glucose concentrations rose significantly in both fed (P less than 0.001) and starved (P less than 0.001) animals [27].
• 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 [28].

References