Disease relevance of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• Gold-thioglucose (GTG) induces lesions in the ventromedial nucleus of the hypothalamus, resulting in hyperphagia and obesity [1].
• Thus, in muscles of gold-thioglucose-obese mice work-induced hypertrophy increased the response to maximal insulin concentrations without modifying the altered insulin sensitivity and decreased insulin binding [2].
• These nodes, the basomedial hypothalamus and the vagal complex of the medulla, seem to share similar biochemical specializations reflected in susceptibility to goldthioglucose toxicity, specific insulin binding, and susceptibility to alloxan diabetes [3].
• In all models, the mature rat, the goldthioglucose-induced obese mouse, and the ventromedial hypothalmic lesioned obese rat, food intake and body weight gain were reduced signficantly by the chronic oral administration of a nontoxic dose of (--)-hydroxcitrate [4].
• BRL 26830A reduced body weight or weight gain in genetically (ob/ob), goldthioglucose, and cafeteria diet obese mice and genetically obese (fa/fa) Zucker rats [5].

High impact information on 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• The level of Ob-Rb in hypothalamus is reduced in mice rendered obese by gold thioglucose (GTG), which causes hypothalamic lesions [6].
• The obesity in GTG-treated mice is likely to be caused by ablation of Ob-Rb-expressing neurons, which results in leptin resistance [6].
• Insulin and insulin-like growth factor I. Effects on protein synthesis in isolated muscles from lean and goldthioglucose-obese mice [7].
• Liver, aorta, and skeletal muscle of ob/ob mice, and mice made obese and hyperinsulinaemic by injection of gold-thioglucose contained greater amounts of farnesylated p21Ras than tissues of their lean normoinsulinaemic counterparts [8].
• The pancreatic content of somatostatin, insulin, and glucagon and the hypothalamic content of somatostatin were examined in ob/ob mice at various ages and in goldthioglucose-obese mice [9].

Chemical compound and disease context of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• Tissue differences in the response of the pyruvate dehydrogenase complex to a glucose load during the development of obesity in gold-thioglucose-obese mice [10].
• Perphenazine-induced PRL release in normal mice and in GTG-injected non-obese mice was compared to that of GTG-injected obese mice after the initial development of obesity, after body weight reduction by diet control and after the resumption of obesity by ad lib. feeding [11].
• We found that hyperphagia was restored and weight loss abolished in anorexic GTG-treated obese adrenalectomized mice after a single icv injection of adrenal glucocorticoids; the dose of cortisone required was found to be 1/60th of that previously shown to be needed systemically to restore hyperphagia [12].
• Vitamin E status in gold-thioglucose-treated obese mice: the influence of weight loss [13].
• Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice [14].

Biological context of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• These early and diverse changes in PDHa argue for a multifactorial aetiology in the development of the whole-body insulin resistance seen in older gold-thioglucose-treated obese animals [15].
• Examples of the latter include a) augmentation of goldthioglucose neurotoxicity, b) induction of hypothalamic anovulation and reproductive failure, c) exacerbation of porphyric encephalopathy, and d) potentiation of parkinsonism and other free radical-related neurodegenerations [16].
• Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver [17].
• In order to determine the effect of inflammation on brain glycolysis in the absence of leukocyte infiltration, [14C]deoxyglucose autoradiography and hematoxylin-eosin (HE) counter-staining were applied to mice at various times after the induction of chemotoxic inflammatory brain lesions by the systemic administration of goldthioglucose [18].
• All mammalian thioredoxin reductase isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs [19].

Anatomical context of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• To find genes differentially expressed in adipose tissue during obesity, we performed suppression subtractive hybridization on epididymal fat mRNA from goldthioglucose (GTG) obese mice and from their lean littermates [20].
• The data suggest that the absence of blood-brain barrier in these sites plays a role in the production of lesions, at least in the initial stages, as has been proposed for goldthioglucose lesions [21].
• The distribution of the lesions in the hypothalamus was similar to that produced by goldthioglucose, and consisted ultrastructurally of marked distention and edema of the extracellular space, with no confined to the dorsal aspect, in the region of the area postrema [21].
• The amount of pyruvate dehydrogenase in the active form (PDHa) was increased 1.7-fold compared with controls in heart muscle of mice 1 week after induction of obesity with a single injection of gold-thioglucose [15].
• The proportion of pyruvate dehydrogenase (PDH) complex in the active dephosphorylated form was decreased (compared with fed lean control mice) in heart muscle mitochondria after the induction of obesity with gold-thioglucose (by 54%) or starvation of lean mice for 48 h (by 81%) [22].

Associations of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol with other chemical compounds

• Perphenazine-induced PRL levels in mice rendered obese with GTG were much greater (2-3 times higher than normal) [11].
• Basal levels of serum PRL and GH were generally lower in gold thioglucose (GTG) and bipiperidyl mustard (BPM)-treated obese mice compared with lean controls [23].
• Inactivation of pyruvate dehydrogenase complex in heart muscle mitochondria of gold-thioglucose-induced obese mice is not due to a stable increase in activity of pyruvate dehydrogenase kinase [22].
• Plasma triglyceride levels significantly decreased (P < 0.02) in NZO, GTG and db/db mice, but not in other obese mice [24].
• The effect of a supraphysiological concentration of insulin on gluconeogenesis from L-[U14C] lactate was studied in hepatocytes isolated from control mice and mice made obese by a single injection of gold-thioglucose (GTG) [25].

Gene context of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin [26].
• GTG injection resulted in approximately 30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls [27].
• Following the chemically-induced lesion of the ventromedial nucleus, gold-thioglucose treated rodents display hypothalamic leptin resistance, hyperphagia, hyperinsulinemia and obesity [28].
• Adiponectin Expression is Paradoxically Increased in Gold-thioglucose-induced Obesity [28].
• We measured activity of peroxisomal acyl CoA oxidase (ACO) in livers, hearts and rectus femoris muscles of gold-thioglucose treated obese mice (n = 17) and control mice (n = 8) [29].

Analytical, diagnostic and therapeutic context of 2-mercapto-6-methylol-tetrahydropyran-3,4,5-triol

• METHODS: Sixty-eight ApoE(-/-) mice were allocated into a control group (n=20), a GTG-injected group (n=28), and a food-restricted group (n=20) [30].
• This produced hyperphagia and obesity: 7 weeks after treatment, those receiving goldthioglucose weighed 70% more than the controls [31].
• We studied the incorporation of dietary n - 3 fatty acids from marine oils into red cell membranes, using animal models of type 1 diabetes (streptozotocin-treated Wistar rats) and type 2 diabetes (gold-thioglucose-injected CBA/T6 mice) [32].
• In the present study, we investigated the effects of goldthioglucose (GTG), a toxic form of glucose, on the expression of the MCH gene in the rat lateral hypothalamus by immunocytochemistry, in situ hybridization and competitive RT-PCR [33].
• Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress [34].

References