Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas total cardiac glycogen phosphorylase activity appears to be unaffected by severe insulin deficiency, a diabetes-induced decreased in hepatic glycogen phosphorylase activity has been demonstrated by our laboratory and others using liver extracts, isolated perfused liver, and cultured hepatocytes. The loss of activity in diabetic liver can be correlated with a drop in protein levels. Using primary cultures of cells from normal and diabetic rats and phosphorylase specific antibodies, we found a corresponding decrease in phosphorylase synthesis in diabetic hepatocytes cultured for 2 days in a serum-free, chemically defined medium. When hepatocytes are cultured in the presence of insulin, triiodothyronine, and cortisol, there is a significant recovery in the rate of phosphorylase synthesis after 3 days. Over the 3-day time period, there is no significant difference in the rate of phosphorylase degradation in normal compared with diabetic hepatocytes. Total protein synthesis in both hepatocytes and cardiomyocytes is unaffected by diabetes, as is phosphorylase synthesis in cultured cardiomyocytes.
 ...
PMID:Phosphorylase synthesis in diabetic hepatocytes and cardiomyocytes. 266 20

1. Hearts of diabetic rats gradually accumulate glycogen, although the activities of glycogen synthase and glycogen phosphorylase are altered in favor of a depletion of glycogen. 2. Phosphorylase in diabetic hearts has been reported to be even more activated in response to adrenaline than controls. 3. The situation is further complicated by the fact that in rat heart two isoenzymes of phosphorylase are present. Therefore we have studied the properties of phosphorylases purified from diabetic rat heart in more detail. 4. This investigation revealed that compared to controls: (A) the amount of enzyme protein which could be isolated from diabetic animals is drastically lower; (B) the affinities towards glycogen and inorganic phosphate are decreased; (C) the activation by phosphorylase kinase is delayed; and (D) the inactivation by protein phosphatase-1 is accelerated. 5. We conclude that all of the reported changes in diabetes might contribute to a phosphorylase system less able to catalyze glycogen breakdown effectively.
 ...
PMID:Activation and inactivation of glycogen phosphorylase isoenzymes purified from diabetic rat heart. 274 7

Two broad-specifically protein phosphatases, termed protein phosphatase-1 (PrP-1) and protein phosphatase-2A (PrP-2A), accounting for all the hepatic activity regulating glycogen phosphorylase, were measured in spontaneously diabetic Chinese hamsters exhibiting persistent glycosuria. When compared with genetically related inbred sublines free of glycosuria, diabetic animals demonstrated approximately 25% increase in PrP-1 activity measured either in crude tissue extracts or in cytosols fractionated by ion-exchange chromatography. No significant alteration in total PrP-2A activity was observed in the diabetic animals. These findings indicate that a specific change in hepatic PrP-1 is associated with genetically acquired diabetes in Chinese hamsters. In contrast to reported data using animals with experimentally induced diabetes mellitus, hepatic PrP-1 was increased in the spontaneously diabetic Chinese hamsters. The data suggests that distinct alterations in PrP-1 and associated metabolic consequences are exhibited by different types of diabetes.
 ...
PMID:Increase in liver protein phosphatase-1 in spontaneously diabetic Chinese hamsters. 303 94

The effects of daily oxytetracycline treatment on the activities of hepatic glycogen synthase, glycogen phosphorylase, plasma glucose, and insulin, and on liver glycogen, free fatty acid, and triglyceride levels were examined in 8- to 15-week-old genetically diabetic and lean mice. Oxytetracycline administration resulted in substantial reductions in the plasma glucose and immunoreactive-insulin levels in both diabetic and lean mice. The drug had no significant effect on the liver glycogen content in either phenotype, regardless of age, but it increased hepatic lipids and depressed body weights in lean animals. The most prominent effect of the drug was in markedly altering the activities of both glycogen synthase and phosphorylase in the liver of older diabetic mice. Oxytetracycline treatment produced a three-fold increase in the percentage of glycogen synthase I activity and reduced by one-third the percentage of glycogen phosphorylase a activity in 15-week-old diabetic mice. In age-matched lean mice treated with oxytetracycline, the percentage of glycogen synthase I activity increased significantly, but the percentage of phosphorylase a activity was unchanged. These data suggest that the drug may alter an aspect of hepatic glycogen metabolism which might lead to an inhibition of glycogenolysis and subsequent diminution of blood sugar levels in the diabetic. The present results show that, while oxytetracycline may be effective in reducing the severity of some of the diabetic symptoms associated with carbohydrate metabolism in this animal model of maturity-onset diabetes, the drug may have adverse effects on aspects of protein and lipid metabolism in these animals.
 ...
PMID:Effects of oxytetracycline treatment on enzymes of hepatic glycogen metabolism in genetically diabetic (db/db) mice. 310 60

In rat hepatocytes, the basal glycogen synthase activation state is decreased in the fed and diabetic states, whereas glycogen phosphorylase a activity decreases only in diabetes. Diabetes practically abolishes the time- and dose-dependent activation of glycogen synthase to glucose especially in the fed state. Fructose, however, is still able to activate this enzyme. Glycogen phosphorylase response to both sugars is operative in all cases. Cell incubation with the combination of 20 mM glucose plus 3 mM fructose produces a great activation of glycogen synthase and a potentiated glycogen deposition in both normal and diabetic conditions. Using radiolabeled sugars, we demonstrate that this enhanced glycogen synthesis is achieved from both glucose and fructose even in the diabetic state. Therefore, the presence of fructose plays a permissive role in glycogen synthesis from glucose in diabetic animals. Glucose and fructose increase the intracellular concentration of glucose 6-phosphate and fructose reduces the concentration of ATP. There is a close correlation between the ratio of the intracellular concentrations of glucose 6-phosphate and ATP (G6-P/ATP) and the activation state of glycogen synthase in hepatocytes from both normal and diabetic animals. However, for any given value of the G6-P/ATP ratio, the activation state of glycogen synthase in diabetic animals is always lower than that of normal animals. This suggests that the system that activates glycogen synthase (synthase phosphatase activity) is impaired in the diabetic state. The permissive effect of fructose is probably exerted through its capacity to increase the G6-P/ATP ratio which may partially increase synthase phosphatase activity, rendering glycogen synthase active.
 ...
PMID:Glycogen synthesis from glucose and fructose in hepatocytes from diabetic rats. 314 17

The concentrations of glycogen phosphorylase protein were determined by rocket immunoelectrophoresis in liver extracts from rats that had artificially induced altered hormonal patterns. These levels were compared with measurements of total phosphorylase activity. Minipump-induced chronic hyperglucagonemia and streptozotocin-induced diabetes resulted in 47% and 67% decreases, respectively, in total phosphorylase activity along with corresponding 52% and 68% drop, respectively, in phosphorylase protein levels. Insulin replacement in diabetic rats returned both parameters to control values. Minipump-induced hyperinsulinemia or injection of glucagon antiserum, T3, or propylthiouracil had no effect. The results of this study indicate that conditions which lead to an elevation of the glucagon to insulin molar ratio to values higher than 1.0 cause a significant decrease in the liver phosphorylase protein level.
 ...
PMID:Regulation of rat liver glycogen phosphorylase concentration by in vivo relative levels of glucagon and insulin. 329 37

The effects of enteric galactose alimentation on neonatal glucose turnover and hepatic glycogen synthesis were investigated in a newborn animal model of diabetic pregnancy. Control pups and pups of diabetic dogs were studied in the basal state and after each group of pups was randomly fed equivalent amounts of galactose or glucose by oral-gastric tubes. Basal fasting blood glucose levels were not statistically different between the groups, whereas basal plasma insulin levels were 2-3 times higher in pups born to diabetic mothers. Blood glucose levels at each time point in response to glucose or galactose feeding in pups of diabetic mothers were not statistically different; however, the rise of plasma insulin concentrations was attenuated in pups of diabetic mothers fed galactose. The increase in the systemic rate of appearance of glucose and in glucose clearance were attenuated in pups of diabetic mothers fed galactose compared with those fed glucose. Hepatic glycogen content was augmented above basal levels in pups of diabetic mothers. Although glycogen synthase activity was not different between glucose- or galactose-fed pups of diabetic mothers, the active component of glycogen phosphorylase was reduced by both glucose and galactose feedings. Galactose alimentation had a greater effect on glycogen phosphorylase than did glucose alimentation. The observed increase in glycogen synthesis and reduced systemic glucose appearance after galactose alimentation could not be accounted for by the previously proposed excess of galactokinase over glucokinase activities when the latter enzyme was assayed at saturation. Indeed, neonatal hepatic glucokinase activity appeared to be induced during diabetic pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Nov
PMID:Galactose assimilation in pups of diabetic canine mothers. 331 54

The role of fetal insulin in placental glycogen accumulation, which occurs despite insulin deficiency in maternal diabetes, was studied in rats. Streptozotocin was injected into fetuses of non-diabetic and streptozotocin-diabetic mothers on days 19.5 and 20.5 of gestation, causing fetal hypoinsulinaemia and pancreatic insulin depletion. Placental glycogen content of either 1.6 mg/g in non-diabetic rats or 6.5 mg/g in diabetic rats was not affected by fetal streptozotocin treatment. Glycogen distribution was also measured in the placenta to assess the effect of fetal hypoinsulinaemia on glycogen content in its fetal segment. The glycogen concentration ratio between the fetal and maternal segments in diabetic rats was approximately 0.3 and increased to approximately 0.5 in diabetic rats, without being affected by fetal hypoinsulinaemia. There was no significant effect of fetal hypoinsulinaemia on the activities of placental glycogen synthase or glycogen phosphorylase, both in non-diabetic and diabetic rats. Fetal hypoinsulinaemia was associated, however, with a marked decrease in fetal liver glycogen together with a decrease in fetal liver weight, which was more pronounced than the decrease in fetal body weight. Administration of insulin to the streptozotocin-treated fetuses restored the impaired glycogen synthesis (measured by incorporation of U-[14C]-glucose and 3H2O in the fetal liver) without affecting glycogen synthesis in the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fetal diabetes in rats and its effect on placental glycogen. 392 71

This study was initiated to determine whether glycogen phosphorylase activation was defective in hearts of alloxan diabetic rats. When hearts were perfused by gravity flow for 1 to 10 min with various concentrations of epinephrine, activation of glycogen phosphorylase in the diabetic was significantly greater at every time and epinephrine concentration than that seen in the normal. Cyclic AMP accumulation and protein kinase activation by epinephrine in the diabetic were not appreciably different or were lower than the normal responses to the hormone. The effects of epinephrine on cAMP and protein kinase were blocked in both normal and diabetic hearts by propranolol. While the beta blocker prevented phosphorylase activation in the normal hearts, it did not block phosphorylase activation by epinephrine in the diabetic hearts. Likewise, the alpha agonist phenylephrine activated phosphorylase in the diabetic but not in the normal hearts. While glucagon produced the same phosphorylase hypersensitivity in diabetic hearts, the cAMP and protein kinase responses were not altered by diabetes. Phosphorylase phosphatase activity was found to be unaltered by either epinephrine or diabetes, whereas phosphorylase kinase activation by epinephrine in the diabetic was double the normal response. These data are consistent with a diabetes-related unmasking of an alpha effect on cardiac phosphorylase activation and an unexplained increase in the sensitivity of phosphorylase kinase activation by protein kinase.
 ...
PMID:A hypersensitivity of glycogen phosphorylase activation in hearts of diabetic rats. 625 85

The effects of diabetes on hepatic carbohydrate metabolism were investigated in spontaneously diabetic Bio-Breeding Worcester (BB/W) rats. The juvenile-onset-type syndrome displayed by these animals is characterized by beta-cell destruction with subsequent ketosis-prone insulinopenia. Livers from diabetic animals demonstrated increased adenosine 3',5'-cyclic monophosphate levels but subnormal total protein and glycogen content. Isolated perfused livers of diabetic BB/W rats demonstrated an increased rate of glucose production from [14C]lactate and an impaired rate of glycogen synthesis. These data were consonant with hepatic enzyme studies demonstrating markedly increased activities of component gluconeogenic (glucose-6-phosphatase, fructose-1,6-diphosphatase, phosphoenolpyruvate carboxykinase) and glycogenolytic (glycogen phosphorylase) enzymes with decreased activities of glycolytic (hexokinase, pyruvate kinase) and glycogenic (glycogen synthase) enzymes. These findings agree with previous studies using alloxan- and streptozotocin-induced diabetic animals and suggest that accelerated hepatic gluconeogenesis and impaired glucose utilization are pathognomonic of all insulin-deficient diabetic syndromes.
 ...
PMID:Hepatic carbohydrate metabolism in the spontaneously diabetic Bio-Breeding Worcester rat. 625 45


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