Subcellular localization of gold in suprarenal testicle and thyroid glands after injection of allochrysine in rats.

Gold injected under the form of anti-rheumatoid polyarthritis soluble solutions provokes, as observed by electron microscope, a deposit of crystalline micro-needles in different tissues, like in cells of adrenal and suprarenal glands, in Leydig cells of the testicles, in isolated thyrocytes and in thyroid endothelial cells. They are present as bundles, often of incurvated type, of high electron-density, present in lysosomes, which contain moreover a hyaline, emptied vesicle. These structures are named "aurosomes". The microanalysis, using the MS 46 (Cameca) and the Camebax (MBX) demonstrates that these crystalline structures are composed by gold associated with sulphur, and not with phosphate.

Development of gluconeogenesis from different substrates in newborn rabbit hepatocytes.

The rates of glucose production from various substrates entering gluconeogenesis at different steps were investigated in hepatocytes isolated from term-fetus and newborn rabbits fasted during the first 2 days of life. The data were compared to the rate of glucose production measured in hepatocytes from young rabbits (50-60 days) starved for 48 h. The net production of glucose from substrates (lactate, pyruvate, propionate, alanine) entering gluconeogenesis below phosphoenolpyruvate was very low at birth and increased during the first day of life, in relation with an increased cytosolic phosphoenolpyruvate carboxykinase activity. The net production of glucose from precursors entering gluconeogenesis at the level of triose phosphates (dihydroxyacetone, fructose) was low at birth but a maximal capacity for gluconeogenesis was reached within 6 h after birth. This enhanced gluconeogenic capacity was associated with a fall in hepatic fructose 2,6-bisphosphate concentration and a reduced glycolytic flux. In contrast, a high glucose production from galactose was already present at birth and did not rise at 24 or 48 h after delivery. These results suggest that the development of gluconeogenic capacity in hepatocytes isolated from newborn rabbit is dependent upon two factors, a decrease in the F2,6-P2 concentration which reduces the glycolytic flux and an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase.

Hepatic triglyceride hydrolysis and development of ketogenesis in rabbits.

Ketogenesis from endogenous fatty acids or exogenous oleate plus carnitine has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. During the first 48 h after birth, hepatic triacylglycerol stores decrease by 80%. The hydrolysis of hepatic triacylglycerol stores has been studied in isolated hepatocytes from 24-h-old fasting rabbits by using lysosomal acid lipase inhibitors and lysosomotropic agents. Their addition decreases the rates of ketone body production by 60-70%, suggesting that hepatic triacylglycerol hydrolysis proceeds via an acid lipase located in the lysosomes. Whereas the rates of ketogenesis from endogenous or exogenous fatty acids are very low in isolated hepatocytes from fetal rabbit, an eightfold increase in the rate of ketogenesis occurs between 6 and 24 h after birth; furthermore the hydrolysis of triacylglycerol stores is sufficient to support the ketogenic capacity in the hepatocytes isolated from 24-h-old rabbits. The emergence of ketogenesis in newborn rabbit hepatocytes is triggered by birth-associated factors rather than to an accurate stage of fetal maturation. Fatty acids are mainly oxidized in the mitochondria because peroxisomal oxidation does not exceed 10-15% of the overall beta-oxidation. Isolated hepatocytes incubated with [1-14C]oleate exhibit at birth a preferential channeling of fatty acid into esterification (93% of oleate metabolized) rather than into oxidation. Conversely oleate oxidation represents 50% of total oleate metabolized 24 h after birth. Factors involved in this switch on of the partition of oleate into esterification and oxidation during the 1st day after birth are discussed.

Development of gluconeogenesis in isolated hepatocytes from the rabbit.

Gluconeogenesis from 10 mM lactate has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. Gluconeogenesis proceeds to a very low rate in fetal rabbit hepatocytes despite substantial activities of all gluconeogenic enzymes including mitochondrial phosphoenolpyruvate carboxykinase. A tenfold increase in the rate of gluconeogenesis occurs in hepatocytes from 1- or 2-day-old fasting or suckling newborn rabbits. The emergence of gluconeogenic capacity in newborn rabbit hepatocytes is triggered by birth itself and not by a chronological factor, and it is primarily controlled by an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase. Moreover, an active fatty acid oxidation is essential to support a high rate of gluconeogenesis in hepatocytes from newborn rabbits.

Relationship between ketogenesis and gluconeogenesis in isolated hepatocytes from newborn rats.

In hepatocytes from 1-day-old rats, active gluconeogenesis occurs in parallel with active ketogenesis, although the carbon atoms of non-esterified fatty acids do not participate in glucose synthesis. Once a significant ketogenesis is established, a further increase does not enhance gluconeogenesis. Indeed, octanoate is more ketogenic than oleate, but stimulates gluconeogenesis to a similar extent.