Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inappropriate overproduction of glucose by the liver is one of the key contributors to the hyperglycaemia of the diabetic state, and thus is a logical site of intervention for novel anti-diabetic approaches. Metformin is the only currently marketed anti-hyperglycaemic drug whose action is attributed largely to its having inhibitory effects on hepatic glucose production, but its molecular site and mechanism(s) of action remain unknown, whereas the liver acting PPAR alpha agonists have their effects primarily on lipid metabolism. This review therefore rather focuses on candidate molecular targets within the liver for anti-hyperglycaemic therapy, and describes potential rate-controlling receptors and enzymes within the glucose producing pathways (glycogenolysis and gluconeogenesis). Most focus is directed towards inhibitors of the enzymes glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase, and towards glucagon receptor antagonists, as these appear to be the most advanced in preclinical and clinical development, although progress with other potential targets is also described. Evidence of the anti-diabetic potential of such agents from animal studies is presented, and the relative merits of each approach are reviewed and compared. It is likely that such agents will become important additions to the therapeutic approaches to combat diabetes.
...
PMID:Pharmacological approaches to inhibit endogenous glucose production as a means of anti-diabetic therapy. 1152 55

We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also examined. The following observations were made: (1) with glucose alone, net glycogen production was low. Inhibition of glucose-6-phosphate translocase increased intracellular glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in active (dephosphorylated) glycogen synthase (GSa) activity, and lactate production (4-fold). With both glucose 6-phosphate translocase and glycogen phosphorylase inhibited, glycogen deposition increased 8-fold and approached reported in vivo rates of glycogen deposition during the fasted-->fed transition. Addition of a physiological mixture of amino acids in the presence of glucose increased glycogen accumulation (4-fold) through activation of GS and inhibition of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased glycolytic flux and increased the flux through glucose 6-phosphatase with no change in glycogen deposition. With glucose 6-phosphate translocase inhibited by S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net glycogen production (1.5-fold), without a major change in GSa activity. It is concluded that glucose cycling in hepatocytes prevents the net accumulation of glycogen from glucose. Amino acids activate GS and inhibit flux through glucose-6-phosphatase, while oleate inhibits glycolysis and stimulates glucose-6-phosphatase flux. Variation in glucose 6-phosphate does not always result in activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids may contribute to the increased hepatic glucose production as seen in Type 2 diabetes.
...
PMID:Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes. 1153 27

We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant reduction in the activities of glucose metabolising enzymes like hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase, fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of blood glucose were also observed in diabetic rats when compared to control rats. The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome-C-oxidase were also significantly lowered in diabetic rats. Molybdate administration to diabetic rats reversed the above changes in a significant manner. From our observations, we conclude that administration of sodium molybdate regulated the blood sugar levels in alloxan-induced diabetic rats. Sodium molybdate therapy not only maintained the blood glucose homeostasis but also altered the activities of carbohydrate metabolising enzymes. Molybdate therapy also considerably improved the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.
...
PMID:Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats. 1183 16

Effect of actoprotector bemitil (2-ethylthiobenzimidazole hydrobromide) on glycogen content and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in cirrhotically altered rat liver. The contents of glycogen and its fraction were determined a cytofluorimetrically (Kudryavtseva et al., 1974). In cirrhosis, the total glycogen content in hepatocytes increases by nearly 3 times, while the amount of a stable fraction of glycogen rises by 7.5 times. Glucose-6-phosphatase activity fell to the level of 25% compare to the norm. Activities of glycogen synthase and glycogen phosphorylase in the cirrhotic liver did not differ from the norm. In cirrhotically altered liver, bemitil produced a decrease in the total glycogen content due to a decrease in glycogen synthase activity in an increase in glucose-6-phosphatase and glycogen phosphorylase activities. The above results suggest a favorable effect of bemitil on cirrhotic liver.
...
PMID:[Effect of bemythyl on carbohydrate metabolism in cirrhotic rat liver]. 1205 67

Short photoperiod induces physiological changes connected to the wintering of the tundra vole, Microtus oeconomus. The aim of the present study was to investigate the effects of continuous melatonin treatment on selected hormones and enzyme activities associated with energy metabolism in the species. Liver, kidney, and muscle glycogen concentrations and glycogen phosphorylase activities, as well as liver and kidney glucose-6-phosphatase and lipase esterase activities were determined. Plasma leptin, ghrelin, thyroxine, testosterone, cortisol, and melatonin concentrations were also measured. Exogenous melatonin stimulated gluconeogenesis, increased glycogen stores, and reduced fat mobilization in kidneys. Melatonin treatment also increased the food intake of the voles. This may have been mediated via elevated ghrelin levels of the melatonin-treated animals, as ghrelin is known to increase appetite of rodents. Winter metabolism of the species does not seem to require accumulation of fat or extra stores of liver or muscle glycogen. On the contrary, successful wintering of the tundra vole presumably depends on continuous food availability.
...
PMID:Melatonin and the wintering strategy of the tundra vole, Microtus oeconomus. 1213 Jul 97

Melatonin affects food intake, body mass and adiposity of several mammals, but the effects of melatonin on energy metabolism remain largely unknown. This study investigated subacute effects of persistent melatonin treatment and continuous light on carbohydrate and fat metabolism of rat liver and kidney. The male and female rats (no.=40) were maintained either in 12L:12D photoperiod or in constant light. Half the rats in both lighting conditions were treated with continuous-release melatonin implants. Liver lipid concentrations, liver and kidney glucose-6-phosphatase, glycogen phosphorylase and lipase esterase activities, glycogen contents as well as plasma T4, T3, insulin, glucose and melatonin concentrations were determined. There was clear sexual dimorphism in the responses to exogenous melatonin and constant light. Continuous light stimulated carbohydrate metabolism of rat liver. Exogenous melatonin enhanced utilization of liver carbohydrates but suppressed hepatic lipolysis. Changes in normal circulating melatonin concentrations led to enhanced utilization of kidney carbohydrates supporting a role for melatonin in renal function. Both exogenous melatonin and constant light seem to have a strong regulatory effect on rat energy metabolism.
...
PMID:Effects of continuous light and melatonin treatment on energy metabolism of the rat. 1224 Sep 4

A number of therapeutic targets are currently under investigation for inhibition of hepatic glucose production with small molecules. Antagonists of the glucagon receptor, glycogen phosphorylase, 11-beta-hydroxysteroid dehydrogenase-1 and fructose 1,6-bisphosphatase are, or have been, under evaluation in human clinical trials. Other strategies, including glucocorticoid receptor antagonists and carnitine palmitoyltransferase inhibitors, are supported by proof of principle studies in man as well as rodents. Several potential targets including glucose-6-phosphatase, glucose-6-phosphatase translocase, glycogen synthase kinase-3, adenosine receptor 2B antagonists, phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase kinase, have been validated by compounds that are effective in animal models. Other targets like PGC-1a and CREB have initial validation support but no medicinal chemistry has been reported.
...
PMID:Potential drug targets and progress towards pharmacologic inhibition of hepatic glucose production. 1257 Jul 14

The effect of the actoprotector bemithyl (2-ethylthiobenzimidazole hydrobromide) on the content of glycogen and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in the cirrhotic rat liver. The content of glycogen and its fraction was determined by a cytofluorimetric method (Kudryavtseva et al. 1974). It has been shown that in cirrhosis the content of total glycogen in hepatocytes increases about 3 times and the content of its stable fraction increases 7.5 times. The activity of glucose-6-phosphatase fell to a level as low as 25% of normal. Activities of glycogen synthase and glycogen phosphorylase in the cirrhotic liver did not differ from normal. In the cirrhotic liver, bemithyl produced a decrease of the total glycogen content which was associated with a decrease of the glycogen synthase activity and an increase of the glucose-6-phosphatase and glycogen phosphorylase activities. Thus, the results of our studies indicate a favorable effect of bemithyl on the cirrhotic liver.
...
PMID:Effects of the 2-ethylthiobenzimidazole hydrobromide (bemithyl) on carbohydrate metabolism in cirrhotic rat liver. 1271 Jul 18

The effect of the administration of blackgram fiber (Phaseolus mungo) on the metabolism of carbohydrates was studied in rats fed 30% NDF (neutral detergent fiber) diet. The experimental group showed a significant increase in liver glycogen level and a significant decrease in blood glucose. Significant increases in the activities of glycogen phosphorylase, hexokinase, fructose-1, 6-diphosphatase, glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase were observed in the experimental group. The activities of phosphoglucomutase and glucose-6-phosphatase were significantly lower in rats fed the fiber diet. The study showed that blackgram fiber exhibits significant hypoglycemic action in experimental animals.
...
PMID:Blackgram fiber (Phaseolus mungo): mechanism of hypoglycemic action. 1285 9

Postmetamorphic South African clawed frogs (Xenopus laevis) were exposed to a phytosterol mixture (ca. 80% beta-sitosterol and less sitostanol, campesterol, and campestanol) for 14 days at 30 mugl(-1) in a flow-through system. The effects of phytosterols (PS) on the plasma thyroid hormone (T(3) and T(4)), testosterone, leptin-immunoreactive peptide and tissue glycogen concentrations were determined. The following enzyme activities were also analyzed from the liver and muscle: glycogen phosphorylase and lipase, and from the liver only: glucose-6-phosphatase. The plasma T(3) concentration was lower in the PS-exposed female frogs. Both muscle lipase and glycogen phosphorylase activities were also lower in the PS-exposed animals. These results could indicate that the basal metabolic rate and locomotion activity of the frogs were decreased. The effects could not be attributed to the possible estrogenicity of the PS mixture. Further studies will be needed to evaluate the possible significance of these effects.
...
PMID:Postmetamorphic Xenopus laevis shows decreased plasma triiodothyronine concentrations and phosphorylase activity due to subacute phytosterol exposure. 1551 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---