Effect of thyroid hormone on blood and liver glucose-6-phosphatase activity

Summary Experimental thyrotoxicosis of mice and rats causes a significant (P<0.01 and P<0.001) rise in hepatic glucose-6-phosphatase activity, but did not affect that of blood plasma. Hepatic alkaline phosphatase activity was raised in thyrotoxic rats, while plasma alkaline phosphatase activity was lowered.(Presented by Member of the Academy of Medical Sciences USSR S. E. Severin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 6, pp. 59–61, June, 1963     

The perinatal development of glucose-6-phosphatase activity distribution pattern in rat liver. A microdensitometrical study

The ontogenetic development of the intralobular distribution pattern of glucose-6-phosphatase activity in the rat liver is described in terms of histochemical changes determined with microdensitometry. A newly developed cerium-lead technique was employed and compared with the common lead technique optimized by Teutsch (1978a). The cerium technique has advantages, meets the prerequisites for quantitative determinations and yields results comparable to biochemically obtained data from microdissected tissue. The first signs of a heterogeneous distribution pattern of glucose-6-phosphatase activity are observed on the 3rd d after birth, and differences between periportal and centrolobular areas are largest around 10th and 15th d. At 30th d after birth, the adult pattern is complete with a centrolobular glucose-6-phosphatase activity of 67% of the periportal value.     

Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation.

1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass.     

High glucose-6-phosphatase activity in osteoblasts in the metaphysis of femur of growing rats

Glucose-6-phosphatase (G6Pase) activity was examined cytochemically in the metaphysis of femurs of 3- and 7-day-old rats. G6Pase and hexokinase activities were also examined biochemically in the femur and tibia of 3-day-old animals. The reaction product for G6Pase activity was seen in the endoplasmic reticulum and nuclear envelope of all cell types composing the metaphysis. The amount of the reaction product was abundant in osteoblasts, moderate in osteocytes, and moderate to scarce in osteoclasts and capillary endothelial cells. Biochemical G6Pase activity in the bones was higher than that in the brain, submandibular gland, or pancreas of the animals. Hexokinase activity in the bones was not different from that in the submandibular gland, pancreas, or kidney. The activity ratio of G6Pase and hexokinase in the bones (0.603) was greater than that in the submandibular gland, pancreas, or brain and smaller than that in the kidney. Possible physiological significances of the higher G6Pase activity in osteoblasts are discussed.     

Effects of fasting and refeeding on the activity of hepatic glucose-6-phosphatase in rats

The activities of glucose-6-phosphate hydrolase and glucose-6-phosphate translocase were determined in rats fasted for 1-3 days and in animals fasted for one day and then either refed with mixed pellet or given oral or intraperitoneal glucose. The assay was based on the colorimetric measurement of the released inorganic phosphate. Fasting over 24 h significantly increased both the translocase and the hydrolase activity of glucose-6-phosphatase. These parameters showed a further increase when rats were fasted for another 24 h. In animals fasted for 24 h and then refed with standardized pellet diet, a progressive fall of enzyme activity was noticed. However, even 72 h of refeeding did not lead to complete normalization. Glucose given orally or intraperitoneally also suppressed the enzyme activity, although the effect was somewhat delayed. As expected, in fasting rats glucose and insulin levels were significantly decreased. Normoglycaemia was established after just 24 h, regardless of refeeding with pellets or with glucose. The former group exhibited hyper- and the latter hypo-insulinaemic pattern. We speculate that augmented activity of hepatic glucose-6-phosphatase during fasting stimulates the metabolism of glucose through the glucose cycle and is thereby at least partially responsible for insulin resistance accompanying the fasting state.     

The microsomal glucose-6-phosphatase enzyme of human gall-bladder

Microsomes isolated from adult human gall-bladders have for the first time been shown to contain specific glucose-6-phosphatase activity. The gall-bladder glucose-6-phosphatase enzyme has the same molecular weight (36,500 daltons) and similar immunological properties and kinetic characteristics to the hepatic microsomal glucose-6-phosphatase enzyme.     

Islet graft-induced changes of beta-hydroxybutyrate dehydrogenase and glucose-6-phosphatase activity in liver cells of diabetic recipient rats.

It is known that the liver is a favourable site for implantation of pancreatic islets since the grafted islets remain metabolically intact and provide long-term normoglycemia in diabetic animals. However, the long-term effects exerted by the grafted tissue on the host organ are not well defined. We therefore investigated by light and electron microscopy the effects of syngeneic islets on the host organ after intraportal transplantation into the liver of streptozotocin (STZ)-induced diabetic LEW.1W rats. In addition, tissue sections of graft-bearing liver were stained by enzyme histochemical methods for beta-hydroxybutyrate dehydrogenase (HBDH) and glucose-6-phosphatase (G6Pase). At 12 weeks after transplantation, the changes seen in the hepatocytes surrounding the grafted islets were hyperproliferation and accumulation of glycogen. Hepatocytes adjacent to the implanted islets displayed increased HBDH activity, whereas G6Pase activity was variable, either decreased or increased. Increased HBDH activity was also observed in the periportal region and in liver cells extending to the central veins. The results demonstrate that intraportal islet grafts, in addition to normalizing glucose homeostasis, exert remarkable effects on the liver parenchyma of experimentally diabetic recipient rats.     

Demonstration of glucose-6-phosphatase and peroxisomal catalase activity by ultrastructural cytochemistry in oval cells from livers of carcinogen-treated rats.

Oval cells isolated from livers of carcinogen-treated rats have morphologic and biochemical features of immature hepatocytes but seem to lack glucose-6-phosphatase (G6Pase) activity. The authors reinvestigated this question using histochemical methods for visualization of G6Pase activity by light and electron microscopy and the polyene antibiotic filipin to facilitate the penetration of the substrate. Oval cells that proliferate in the liver of animals receiving a carcinogenic diet (choline-deficient, containing 0.05% ethionine) contained G6Pase activity; 50-60% of nonparenchymal epithelial cells isolated from these livers by centrifugal elutriation contained G6Pase activity; and oval cell cultures displayed intense G6Pase activity at confluence but did not have detectable enzyme activity during exponential growth. These results and the demonstration that clofibrate induces peroxisomal proliferation in cultured oval cells strengthen the view that oval cells (or some subpopulation of cells in this compartment) are part of the hepatocyte lineage.     

Decrease of the inhibition of lipid peroxidation by glutathione-dependent system in erythrocytes of non-insulin dependent diabetics

Summary The inhibition of lipid peroxidation of erythrocyte membranes by glutathione-dependent protection was studied in patients with non-insulin dependent diabetes mellitus. Incubation of red cells from diabetics with 1.5 mM t-butyl hydroperoxide resulted in a lipid peroxidation increase greater than that of normal controls. Glutathione-dependent and glutathione-independent protection against oxidative damage was examined using an artificial system, in which erythrocyte ghosts were incubated with t-butyl peroxide and dialysed hemolysate in the presence or the absence of 2 mM glutathione. The glutathione-dependent protection of hemolysate from diabetics was approximately 70% of that from normal controls.The results suggest that decrease in glutathione-dependent protection against lipid peroxidation, along with decrease in glutathione levels, increases oxidative damage in erythrocyte membranes taken from diabetic patients.Abbreviations GSH reduced form of glutathione - GSSG glutathione disulfide - TCA trichloracetic acid - SOD superoxide dismutase - GPX glutathione peroxidase - MDA malondialdehyde