Disease relevance of Alloxan

• Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy [1].
• However, since it has been reported that fat, muscle, and hepatic tissue from rats made diabetic by alloxan administration are insensitive to insulin, the capacity for binding can not be the sole factor determining the response to insulin in diabetes mellitus [2].
• Alloxan-diabetic rabbits develop a pronounced hypercholesterolemia and hypertriglyceridemia in response to cholesterol feeding [3].
• We have assessed the susceptibility to arrhythmias in a canine model after 1 yr of mild diabetes induced by alloxan [4].
• Determinants of the selective toxicity of alloxan to the pancreatic B cell [5].

Psychiatry related information on Alloxan

• In the present study, pain threshold was assessed via tail flick latency in alloxan-diabetic and control rats [6].
• Effects of alloxan induced diabetes on the feeding patterns of rats [7].
• Furthermore, the amphetamine resistance appears to be the result of the diabetic state, since amphetamine-induced stereotyped behavior could be reinstated in alloxan-injected rats by the administration of protamine zinc insulin for ten days [8].
• This conclusion was supported by further experiments indicating that alloxan-injected rats show diminished locomotor activity and stereotyped behavior following amphetamine administration [8].

High impact information on Alloxan

• Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets [9].
• We therefore administered small quantities of alloxan into the cerebrospinal fluid of rats to determine what effect this might have on their ability to react to changes of glucose concentration [10].
• An artificial pancreas consisting of beta cells cultured on synthetic semipermeable hollow fibers was tested in rats with alloxan-induced diabetes [11].
• This specificity suggests that the beta cell membrane is extremely stereospecific, and that glucose or 3MG provide protection against alloxan injury directly by an interaction with the cell membrane and not by subsequent metabolism of the protecting compound [12].
• To evaluate the importance of islet cells in the development of autoimmunity in the nonobese diabetic (NOD) mouse, we generated beta cell-deprived mice by injecting a high dose of alloxan, a toxic agent specific for beta cells [13].

Chemical compound and disease context of Alloxan

• Thus, alloxan showed an apparent Km of 70 microM in the presence of 3.4 microM E. coli thioredoxin, 0.2 microM thioredoxin reductase, and 0.4 mM NADPH [14].
• Supplementation with N-acetylcysteine (NAC, 500 mg/kg), a GSH precursor, inhibited alloxan-induced NFkappaB activation and reduced hyperglycemia [15].
• Indeed, both hyperinsulinemia and impaired glucose tolerance developed spontaneously between 6 and 8 weeks of age in alloxan-untreated males [16].
• Nicotinamide, a poly(ADP-ribose)synthetase inhibitor, protected NMRI mice against alloxan-induced hyperglycemia when given 10 min before, but not 10 min after, the injection of the drug [17].
• Streptozocin (STZ) and alloxan (ALX) exhibit the most potent diabetogenicity and are used for induction of experimental diabetes mellitus [18].

Biological context of Alloxan

• High affinity binding sites of islets from rats pretreated with alloxan decreased by about one half, whereas Kd was unaffected [19].
• We therefore studied the effects of DIMIT (0.5 mg/kg per d, s.c.) administration to pregnant alloxan-diabetic rabbits on days 25 and 26 of gestation [20].
• The involvement of tyrosine phosphorylation in insulin action led us to hypothesize that increased activity of protein tyrosine phosphatases (PTPases) might contribute to insulin resistance in alloxan diabetes in the rat [21].
• This hydrolysis was inhibited by alloxan but unaffected by dextran of NaF [22].
• Type I diabetes mellitus was induced in male rats by alloxan (140 mg/kg, i.p.). After 5 wk, the diabetic rat penis exhibited increased O-GlcNAc modification of eNOS and decreased eNOS phosphorylation at Ser-1177 at baseline compared with the control rat penis; eNOS phosphorylation at Thr-495, Ser-615, and Ser-633 was not affected [23].

Anatomical context of Alloxan

• Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats [24].
• Alloxan-diabetic mice bearing a subcapsular islet graft insufficient to normalize the blood glucose level were rendered normoglycemic by a second intrasplenic islet graft after various period of hyperglycemia to examine the reversibility of hyperglycemia-induced B cell dysfunction [25].
• A decrease in Na(+)-K+ ATPase activity (42%; P less than 0.05), only seen in the presence of endothelium, was also observed in aortas taken directly from alloxan-induced diabetic rabbits [26].
• The diabetogenic agent alloxan exerts a preferential cytotoxic effect on the pancreatic B cell [5].
• However, E. coli and calf thymus thioredoxin-(SH)2 both efficiently reduced alloxan [14].

Associations of Alloxan with other chemical compounds

• Hepatic protein phosphotyrosine phosphatase. Dephosphorylation of insulin and epidermal growth factor receptors in normal and alloxan diabetic rats [27].
• After 5-8 days in tissue culture, human or rodent islets were exposed for 14 h to NP (50-200 microM) or for 30 min to SZ or alloxan (1-3 mM) [28].
• At 3 days after alloxan injection (DIAB-3 group) both taurocholate maximum secretory rate and pool size were significantly decreased, whereas they were restored to normal values after 6 days of diabetes (DIAB-6 group) [29].
• Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors [30].
• The possible participation of superoxide anions, hydrogen peroxide, and hydroxyl radicals in the action of alloxan was investigated using isolated rat pancreatic islets [31].

Gene context of Alloxan

• Endogenous accumulation of H2O2/ROSs in macrophages treated with alloxan resulted in IL-12 p40 inhibition [32].
• Female C57BL/6J mice, either with or without the Sp allele, were injected intravenously with alloxan (100 mg/kg), and plasma glucose was measured 3 days later [33].
• In the present study, we tested whether ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a glutathione peroxidase mimicking compound, could counteract the effects of IL-1 beta, H2O2 and alloxan in rat pancreatic islets and in the rat insulinoma cell line RINm5F (RIN cells) [34].
• Acute alloxan diabetes was associated with decreased AR in small arteries, but not glomeruli [35].
• Diabetes was induced in Cyp8b1-/- and wild type animals (Cyp8b1+/+) by alloxan, and the mice were fed normal or cholesterol-enriched diet for 10 weeks [36].

Analytical, diagnostic and therapeutic context of Alloxan

• Transplantation of grafts consisting of 3 x 10(5) beta cells (1,000 aggregated) under the kidney capsule of alloxan-diabetic nude mice corrected hyperglycemia in 75% (10/13) of the animals, whereas, 100% (20/20) of recipients implanted with 6 x 10(5) beta cells (2,000 aggregates) achieved euglycemia within 8 wk posttransplantation [37].
• The pattern persists after bilateral transthoracic vagotomy and in animals rendered diabetic by alloxan [38].
• The viability of human beta cells purified by flow cytometry was not affected by SZ or alloxan (5 mM), as judged 1 or 4 days after a 10-min exposure and subsequent culture; these conditions were cytotoxic for rat beta cells, with 65-95% (P < 0.01) dead beta cells after 4 days [28].
• Activation of NFkappaB in pancreatic nuclear extracts was observed 30 min after alloxan injection, as assessed by an electrophoretic mobility shift assay [15].
• Using EPR spin trapping techniques, we demonstrated that alloxan generated ROS in the pancreas 15 min after administration [15].

References