Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycerol, glycerol-3-phosphate (G3P), and dihydroxyacetone phosphate (DHAP) were evaluated as inhibitors of gluconeogenesis on rat liver enzymes in vitro, and for their effects on glucose formation in vivo in well-nourished and malnourished rats. DHAP was more potent as an inhibitor than G3P on fructose-1,6-diphosphatase (FDPase), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase). The I50 for DHAP was 2, 8, and 9 x 10(-3) M, respectively. No effect was observed on rat liver pyruvate carboxylase (PC). Glycerol was a weak inhibitor of FDPase and PEPCK, but did not inhibit PC and G6Pase. In vivo, when G3P was injected before a parenteral L-alanine (Ala) challenge, it produced a hypoglycemic effect in malnourished rats and a lesser, but noticeable, blood glucose level reduction in well-fed animals. Glycerol caused a smaller reduction in glucose formation from Ala. No comparable effects were observed after a fructose pretreatment. These results underscore the potential hypoglycemic effects of phosphorylated glycerol metabolites and identify the steps in gluconeogenesis where this action is exerted. The study also stresses the nutritional component in the glycerol intolerance syndrome, apparent from the far more severe effects observed in malnourished rats given G3P or glycerol prior to Ala.
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PMID:Regulation of gluconeogenesis by glycerol and its phosphorylated derivatives. 298 19

The activities and zonal distribution of key enzymes of carbohydrate metabolism were studied in livers of diabetic rats. 48 h after alloxan treatment the following alterations were observed, intermediate values being reached after 24 h: Blood glucose, acetoacetate and beta-hydroxybutyrate were increased to more than 500%; liver glycogen was reduced to about 10%. Portal vein insulin was reduced to below 10%, portal glucagon was increased to almost 200%. The glucogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were enhanced to 320% and 150%, respectively. The glycolytic enzymes glucokinase and pyruvate kinase L (differentiated from the M2 isoenzyme with a specific anti-L-antibody) were lowered to 50% and 75%, respectively. The citrate cycle enzyme succinate dehydrogenase remained unchanged. The normal periportal to perivenous gradient of phosphoenolpyruvate carboxykinase of about 3:1, as measured in microdissected tissue samples, was enhanced to about 4:1 with activities elevated to 230% and 190%, respectively, in the two zones. The normal periportal to perivenous gradient of pyruvate kinase L of about 1:1.7, as determined with the microdissection technique, was reduced to about 1:1.4 with levels lowered to 55% and 45%, respectively, in the two zones. The even zonal distribution of pyruvate kinase M2 remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic zonation in liver of diabetic rats. Zonal distribution of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucose-6-phosphatase and succinate dehydrogenase. 298 84

The activities and zonal distribution of key enzymes of carbohydrate metabolism were studied in livers of rats after end-to-side portocaval anastomosis. Sham-operated control animals with the same periods of interruption of hepatic blood supply as the shunted animals were pair-fed. The following alterations were observed: Food uptake was reduced to about 20% at the first postoperational day; it was then increased continuously to about 70% at day 8. Body weight, after a small 10% postoperational decrease, remained unaltered, but liver weight was lowered to 55% at day 8 and then stayed constant. The total glycogen reserves of the liver (g X 100 g body weight-1) were reduced, after a transient fall to about 10% at day 1-4, to about 25%. The total activity of the glucogenic phosphoenolpyruvate carboxykinase (mumol . min-1 X 100 g body weight-1) was diminished, after a transient increase to 190% and 150% at day 1 and 2 respectively, to about 55% from day 8 onwards. The total activity of the glucogenic glucose-6-phosphatase was lowered without a transient rise to about 30%. The total activities of the glycolytic pyruvate kinase isoenzyme L and glucokinase were decreased continuously to about 40% at day 8; that of the citrate cycle enzyme succinate dehydrogenase was lowered parallel with liver weight to 55%. The transient decrease of the glycogen reserves and the intermediate increase of the phosphoenolpyruvate carboxykinase capacity were due to the operational stress, since they were observed also in the sham-operated control animals. All other alterations, the decrease of liver weight and of the capacities of both gluconeogenic and glycolytic key enzymes, were specific for the portocaval anastomosis. The normal periportal to perivenous gradient of phosphoenolpyruvate carboxykinase of about 3.5:1, as measured in microdissected tissue samples, remained the same with specific activities reduced to about 80% each in the two zones. The normal periportal to perivenous gradient of pyruvate kinase L of about 1:1.7 was equalized with levels lowered to 35% and 23%, respectively, in the two zones. The normal periportal to perivenous gradients of glucose-6-phosphatase and succinate dehydrogenase, demonstrated histochemically, were essentially maintained with perivenous bridging occurring transiently at day 4 and 8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucostat capacity and metabolic zonation in rat liver after portocaval anastomosis. 299 14

The liver is the "glucostat" of the organism and serves at the same time as an "ammonia-sink and pH stat". The key enzymes involved in glucose uptake and release and in urea and glutamine formation are reciprocally distributed over the liver parenchyma: The glucogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK), fructosebisphosphatase (FBPase) and glucose-6-phosphatase (G6Pase) as well as the ureagenic enzyme carbamoylphosphate synthetase (CAPS) are predominant in the periportal zone. The glycolytic enzymes glucokinase (GK) and pyruvate kinase type L (PKL) as well as the glutaminogenic enzyme glutamine synthetase (GluNS) are prevalent in the perivenous zone. This heterogeneity appears to be a prerequisite for the normal "glucostat, ammonia-sink and pH-stat" function of the liver. After birth the liver is a gluconeogenic organ, only with weaning it becomes a "glycolytic/gluconeogenic" glucostat. In the rat zonation of PEPCK, G6Pase and CAPS developed gradually after birth and was completed before weaning, i.e. before it would be functionally required. After 2/3 partial hepatectomy the liver looses its normal glucostat function and becomes a gluconeogenic organ. With this change the zonation of PEPCK and PKL were also lost; it was restored only during the second week after operation. During starvation the liver also looses its glucostat function to become the major glucose supplier of the organism. Zonation of PEPCK and PKL were diminished to such an extent that the major function of the perivenous zone was altered from glucose uptake to release. In diabetes the liver does not loose its glucostat function; however, the function is severely impaired. Zonation of PEPCK was increased and that of PKL decreased in such a manner that the major function of the perivenous zone, glucose uptake, was not entirely changed but only diminished. It can be concluded that in the various physiological states studied the zonation of enzymes correlated well with the glucostat function of the liver.
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PMID:Dynamics of zonal hepatocyte heterogeneity. Perinatal development and adaptive alterations during regeneration after partial hepatectomy, starvation and diabetes. 301 Mar 76

Triphasic changes in glycogen content and activities of four enzymes of carbohydrate metabolism (glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, hexokinase, and glucose-6-phosphate dehydrogenase) were studied in the liver of male Wistar rats exposed to 1, 5, 10, 15, 20, 30, 45, 60, 70 and 90-day movement restrain in pencil cases. It was assumed that these three phases corresponded to the alarm, resistance and exhaustion stages of Selye's general adaptation syndrome. In hypokinetic rats, however, a transition of the alarm reaction to the resistance stage was registered later, and hepatic glycogen accumulation was reduced in comparison with the standard pattern observed in chronic stress.
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PMID:Effect of prolonged restraint on glycogen content and activities of four enzymes of carbohydrate metabolism in the liver of rats. 301 79

Activities (mumol X min-1 X g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes. Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and beta-hydroxybutyrate being elevated by more than fivefold. Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively. The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocin- and alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones. The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected. Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes. 302 62

Activities of key enzymes of gluconeogenesis--phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, glucose-6-phosphatase as well as the content of glycogen were studied in liver tissue of thymectomized rats. Gluconeogenesis was inhibited in liver tissue of these rats. As thymus and adrenal cortex are firmly related, the inhibition of gluconeogenesis in liver tissue of thymectomized rats appears to occur due to a decrease in the glucocorticoid activating effect followed the inhibition of adrenal cortex functions and absence of thymus hormones directly responsible for carbohydrate metabolism.
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PMID:[Effect of thymectomy on activity of key enzymes of gluconeogenesis in the rat liver]. 303 99

1. The effect of adrenalectomy on the adjustments of carbohydrate metabolism to fasting was studied in rats fed a high-protein, carbohydrate-free (HP) diet. 2. Fasting for 24 h induced a 20% decrease of blood glucose levels in intact rats on the balanced, control (C) diet, but did not affect the blood glucose levels of rats adapted to the HP diet. After adrenalectomy, HP rats lost their capacity to maintain constant blood glucose levels during fasting, but the reduction in blood glucose (30% after 24 h) took longer to appear and was 50% smaller than in adrenalectomized C-rats. 3. Intact rats on the control diet responded to fasting with increased in vitro hepatic gluconeogenic capacity as well as increased phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase activities. Adrenalectomized C-rats also responded to fasting with increased gluconeogenesis and PEPCK activity. In contrast, for both intact and adrenalectomized HP-fed rats, liver gluconeogenesis and PEPCK activity, which were already high in the fed state, did not change or even decreased slightly after fasting. 4. After food restriction, the rates of glucose replacement by adrenalectomized rats on the control diet were higher than those of intact animals on the same diet. This effect was not observed in HP-fed rats, in which the rates of glucose replacement were even slightly lower in adrenalectomized than in intact animals. 5. These data suggest that the mechanism of fasting-induced hypoglycemia after adrenal removal is different for HP and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of adrenalectomy on glucose homeostasis in rats fed a high-protein, carbohydrate-free diet. 369 60

Fetal and maternal sheep were studied to determine whether changes in gluconeogenic enzyme activities could be detected in the liver and/or kidney associated with maternal nutritional deprivation. Thirteen ewes and 16 fetuses were sacrificed in the fed state, while 13 ewes with 17 fetuses were sacrificed after 5 days of fasting, all at 125 days gestation (term = 147 days). Fetal weight was decreased in the fasted versus fed group (2.86 +/- 0.56 versus 3.61 +/- 0.58 kg, p less than 0.001). Tissues were analyzed for glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase, glutamate oxaloacetate aminotransferase, and glutamate pyruvate aminotransferase. In maternal liver, four of the six enzymes increased significantly during fasting, whereas none of the enzymes increased in maternal kidney. In fetal hepatic tissue, five of the six enzymes (with the exception of pyruvate carboxylase) increased during maternal fasting and three of the enzymes increased in renal tissue. These data are consistent with the potential for increased rates of gluconeogenesis in the ovine fetus during periods of compromised maternal nutrition.
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PMID:Effects of fasting on gluconeogenic enzymes in the ovine fetus. 372 67

Hepatic carbohydrate metabolism was studied in adult and suckling rats given age-specific LD50 doses of dieldrin po. These doses in 5-, 10-, and 60-day-old Wistar rats were 38, 28, and 63 mg/kg, respectively. Plasma glucose and free fatty acids (FFA), and hepatic glycogen, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), and glucose-6-phosphatase (G6P) were measured 1 and 3 h after administration of the insecticide. Plasma glucose concentrations were elevated (17%) in some 5-day-old rats after 1 h and in all adults after 1 and 3 h (45 and 30%, respectively). Plasma FFA concentrations were decreased (9%) in the 5-day-old rat 1 h after dieldrin. Hepatic glycogen content was reduced in both 5- and 10-day-old pups at 1 hour (22 and 17%, respectively). Hepatic FDP activity was elevated in the 5-day-old rat at 1 h (17%) and was decreased (10%) in the 10-day-old rat at 3 h. Hepatic PEPCK activity was increased in adult animals by 30% 1 h after dieldrin. Furthermore, PEPCK activity was increased at 3 h in rats of all ages (76%, 5-day-old pup; 115%, 10-day-old pup; 56%, 60-day-old adult). Hepatic G6P activity was unaltered by dieldrin. Thus only the activity of hepatic PEPCK is consistently elevated by dieldrin exposure. However, this enhanced PEPCK activity is associated with dieldrin-induced hyperglycemia only in the adult rat.
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PMID:Effects of dieldrin on hepatic carbohydrate metabolism in the suckling and adult rat. 375 18


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