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)

Cell fractionation, enzyme analysis, and electron microscopy were used to study the effects of streptozotocin-induced diabetes and insulin replacement on liver structure and function. In liver homogenates from diabetic rats, glucose-6-phosphatase (G-6-Pase) activity was stimulated about 2 1/2-fold over that found in normal animals. Analyses of isolated rough and smooth microsomes from diabetic rats for G-6-Pase activity showed a fourfold increase in the smooth microsomes and a small increase in enzyme activity in rough microsomes when compared with these fractions from control animals. Associated with the increased enzyme activity was a reduction in liver glycogen. Insulin treatment of the diabetic rats caused a fall in homogenate G-6-Pase levels to approximately normal values and stimulated the accumulation of hepatic glycogen. Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes. Studies with the electron microscope revealed ultrastructural alterations in livers of the diabetic rats, which were most striking in the periportal region of the lobule. Periportal hepatocytes from diabetic rats displayed dispersed particles of glycogen separated by cytoplasm rich in SER rather than dense masses of glycogen with little SER, as is characteristic of these cells in normal animals. Centrilobular cells from the diabetic animals displayed some disorganization of the RER and a dispersed pattern of glycogen with abundant SER, similar to the pattern found in these cells from normal animals. After insulin treatment the periportal cells appeared normal morphologically, whereas the centrilobular hepatocytes displayed regions of both dense masses and dispersed glycogen. In the glycogen masses, little SER was found; however, in the areas of dispersed glycogen particles, an abundance of this organelle was evident. We conclude from these studies that diabetes causes an increase in amount of hepatic smooth endoplasmic reticulum (SER), especially within periportal hepatocytes. The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase. We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase. It is suggested that this cellular specialization is a response of the hepatocyte to the diabetic state, namely, a demand for increased hepatic glucose production and release into the blood stream, thus contributing to the hyperglycemia characteristic of this disease. Insulin administration to the diabetic animals reverses the above alterations.
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PMID:Hepatic glucose-6-phosphatase activities and correlated ultrastructural alterations in hepatocytes of diabetic rats. 22 Dec 99

We have examined the influence of the phenobarbital-induced proliferation of the hepatic endoplasmic reticulum (ER) on the activities of the components of the glucose-6-phosphatase system, i.e., the enzyme, the glucose-6-P translocase (T1), and the phosphate translocase (T2). Young male rats were injected ip twice daily for 4 days with 4 mg/100 g body wt of phenobarbital (PB) or an equivalent volume of saline solution. On the fifth day, the rats were killed and smooth (SER) and rough (RER) fractions of the ER were isolated from liver homogenates. Kinetic constants for glucose-6-P hydrolysis by the system and enzyme were determined and used to calculate the kinetic constants for glucose-6-P transport. T2 activity was approximated by assaying the pyrophosphatase activity at pH 6.0 in intact microsomes. Three times more SER protein was recovered from livers of PB-treated rats. PB-treatment did not alter total liver enzyme activity, but total liver T1 activity was decreased to 59% of the control value. Maximal specific activities of the system, enzyme and T1 were all reduced by PB treatment to 44% of control values in the RER and to 68% of control values in the SER. PB treatment reduced the apparent activity of T2 in RER and SER to 35 and 49% of the respective control values. In the SER from both groups of rats, T1 activity or apparent T2 activity divided by enzyme activity was about 55% of the corresponding ratio in the RER. Our analysis of these data suggests that the lower activities of T1 and T2 in the smooth ER are the results of suppression by some intrinsic component localized in the smooth membrane. Accordingly, the reduction in total liver T1 activity and, therefore, system activity in PB-treated rats reflects the redistribution of the glucose-6-P translocase from the RER to the more abundant SER membrane where it is less active. The possibility is discussed that a higher cholesterol content within the SER membrane is responsible for the lower transport activities.
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PMID:Phenobarbital-induced alterations in the activities of the transport and hydrolytic components of the glucose-6-phosphatase system in smooth and rough subfractions of the rat hepatic endoplasmic reticulum. 302 67

Administration of N-hydroxy-2-acetylaminofluorene (90 mumol/kg, iv) to rats results in damage to periportal hepatocytes. The most prominent ultrastructural changes are the appearance of numerous unusual vesicles of about 200 nm diameter and the proliferation of the endoplasmic reticulum to form fingerprint-like structures. In order to characterize these vesicles and to investigate their possible origin, their enzymatic activity was studied by ultrastructural enzyme histochemistry. The vesicles as well as the fingerprint-like structures exhibited glucose-6-phosphatase activity. Continuities between the vesicles and the membranes of both the RER and the SER were frequently seen. The vesicles lacked ATPase, 5'nucleotidase and catalase activity. From these results we conclude that the vesicles may be an unusual proliferation of the endoplasmic reticulum.
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PMID:Genesis of unusual vesicles in rat periportal hepatocytes after administration of N-hydroxy-2-acetylaminofluorene. 614 30

Young male Sprague-Dawley rats were injected intraperitoneally with a single dose of aflatoxin B1 (AFB1, 3 mg/kg). At 3, 6, 12, and 24 hours and 1, 2, and 5 weeks, the rats were killed and liver samples were taken for examination of sequential ultrastructural changes and localization of acid phosphatase (AcPase), thiamine pyrophosphatase (TPPase) and glucose-6-phosphatase (G6Pase) activity. At 3-6 hrs of AFB1 treatment, the nucleoli became compacted and the network forms of nucleolonema disappeared. Parallel arrays of rough ER encountered in normal liver cells became deranged. Smooth ER increased to form groups of SER anastomosis or vesicles near the golgi area. At 12-24 hours, disruptions of nucleoli, ER systems, and polysomes became more evident. Parallel arrays of ER membranes, forming whorls in the cytoplasm as well as in the cytoplasmic patches (CP), were G6Pase-positive, although the CP were AcPase-negative. The TPPase reaction in bile canaliculi was frequently diminished, but was present in some measure in the Golgi saccules. By 1-2 weeks, most of the injured cells had recovered gradually. The CP disappeared and parallel arrays of RER were observed again in most parenchymal cells. At 5 weeks, the appearance of the nucleoli was normal, as was that of the other organelles. We concluded that the hepatic parenchymal cells had serious lesions at 12 and 24 hours of AFB1 treatment and then recovered nonsynchronously. The response, resistance, and ability to recover from the toxicity of AFB1 varied among the parenchymal cells. The three marker enzymes persisted throughout all regimens of AFB1 treatment.
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PMID:Cytochemical and ultrastructural changes in aflatoxin-induced injury to rat liver cells. 615 42

The biochemistry and ultrastructure of hepatocytes from streptozotocin-diabetic rats adapted to a controlled feeding schedule are described. The microsomal enzyme glucose-6-phosphatase (G-6-Pase), required for glucose release from the hepatocyte was monitored in homogenate preparations at times after the initiation of feeding in rats trained to a 6 h feeding, 18 h fasting cycle. G-6-Pase specific activity which is increased in ad lib fed diabetic rats was not further increased with time after the initiation of feeding in the feeding trained animals. However, the known elevation in G-6-Pase latent activity of the diabetic rat was reduced during the feeding cycle of times of minimum and maximum plasma glucose. Enzyme latency is a reflection of the multicomponent nature of G-6-Pase activity; therefore, plasma glucose levels may influence elements of that multicomponent system. Hepatic rough and smooth endoplasmic reticulum (RER + SER) fractions from the diabetic animals exhibited high and equivalent G-6-Pase specific activities independent of feeding or fasting. Ultrastructural observations of periportal hepatocytes showed a high content of SER correlated with the high G-6-Pase specific activity and closely associated with dispersed particles of glycogen at all times after the initiation of feeding. Also, an increase in SER was observed in the fasted normal animals although particulate glycogen was nearly absent. These findings support earlier work indicating that diabetes stimulates the proliferation of hepatic SER and that the membranes of this organelle are altered from those of the normal animal.
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PMID:Subcellular responses of hepatocytes to diabetes in control-fed rats. 629 20