Gluconeogenesis and P-enolpyruvate carboxykinase in liver and kidney of long-term fasted quails

The activity of cytoplasmic and mitochondrial phosphoenolpyruvate carboxykinase (PEPCK) in kidney and liver, and in vivo gluconeogenic activity, were determined during different phases of prolonged fasting in quails. The fasting-induced changes in the activity of kidney cytoplasmic PEPCK were positively correlated with the changes in gluconeogenesis. Both activities increased at the initial phase (I) of fasting to levels 65% to 100% higher than fed values, and decreased during the protein-sparing period (phase II), although remaining higher than in fed birds. At the catabolic final phase (III) both kidney cytoplasmic PEPCK activity and gluconeogenesis increased markedly, attaining levels 115% to 150% higher than fed values. The activity of liver cytoplasmic PEPCK, present in appreciable amounts in quails, did not change during phases I and II of fasting, but increased to levels 60% higher than fed values at the final phase (III). Plasma glucose levels at phase III did not differ significantly from those at phases I and II. In both kidney and liver the activity of the mitochondrial PEPCK was not significantly affected by fasting. The data suggest that the kidney cytoplasmic PEPCK is the main enzyme responsible for gluconeogenesis adjustments during food deprivation in quails, and that this function is complemented at the final phase by enzyme present in liver cytosol.

Gluconeogenesis and glucose replacement rate during long-term fasting of Japanese quails

Gluconeogenic activity and kinetic parameters of glucose metabolism were estimated during the different phases of prolonged food deprivation in quails. Gluconeogenic activity, estimated from the rate of increase of incorporation of (HCO3-)-C-14 into circulating glucose, was significantly higher in fasted quails than in fed birds, whatever the period of food deprivation. However, gluconeogenic activity during phase II, although higher than in the fed state, was significantly lower than in quails fasted for 2 days (phase I) or in those on the final (phase III) period of starvation. Gluconeogenic activity did not differ significantly in birds from phases I and III. Rates of glucose replacement, estimated with [6-H-3]-glucose, were very high (20.5 mg . kg(-1). min(-1)) in fed quails and were markedly reduced (to about 42% of fed values) by fasting, no difference being observed between quails fasted for 2 and 5 days. Because of the poor condition of the birds, glucose replacement rates could not be measured during phase III. The present data are the first to provide direct evidence for the changes in gluconeogenesis which occur during prolonged food deprivation.

Fasting, adrenalectomy, and gluconeogenesis in the chicken and a carnivorous bird

Previous studies showed that livers from carnivorous birds have a higher gluconeogenic capacity and higher levels of gluconeogenic enzymes than livers from granivorous birds. In this work we compare the effects of fasting and adrenalectomy on gluconeogenesis. Fasting in the chicken elicited increased rates of incorporation of 14C from alanine into blood glucose, increased gluconeogenesis in liver slices, and increased activities of four gluconeogenic enzymes: glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, alanine aminotransferase, and aspartate aminotransferase. These responses in the chicken resemble those observed in fasted rodents. In marked contrast, fasting in black vultures induced decreased rates of incorporation of alanine label into circulating glucose, decreased gluconeogenesis in liver slices, and no change in any of the four enzymes studied. This unusual response to fasting in the carnivorous bird is probably related to the high-protein-low-carbohydrate content of the diet. Fasted adrenalectomized birds (granivorous and carnivorous) had reduced rates of in vivo glucose synthesis, decreased liver gluconeogenesis, and lower activity of glucose-6-phosphatase and aspartate aminotransferase, without change in phosphoenolpyruvate carboxykinase and alanine aminotransferase activities.

Effect of a meal feeding schedule on hepatic glycogen synthesis and gluconeogenesis in rats

We investigated the effect of a meal feeding schedule (MFS) on food intake, hepatic glycogen synthesis, hepatic capacity to produce glucose and glycemia in rats. The MFS comprised free access to food for a 2-hour period daily at a fixed mealtime (8.00-10.00 a.m.) for 13 days. The control group was composed of rats with free access to food from day 1 to 12, which were then starved for 22 h, refed with a single meal at 8.00-10.00 a.m. and starved again for another 22 h. All experiments were performed at the meal time (i.e. 8.00 a.m.). The MFS group exhibited increased food intake and higher glycogen synthase activity. Since gluconeogenesis from L-glutamine or L-alanine was not affected by MFS, we conclude that the increased food intake and higher glycogen synthase activity contributed to the better glucose maintenance showed by MFS rats at the fixed meal time. Copyright © 2001 National Science Council, ROC and S. Karger AG, Basel.

Hepatic gluconeogenesis in rats trained to eat a single meal daily. Role of eating periodicity and the amount of food ingested in the last meal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cissus sicyoides (princess vine) in the long-term treatment of streptozotocin-diabetic rats

Leaf decoctions of Cissus sicyoides (princess vine) are taken widely as a popular remedy for diabetes mellitus in Brazil, where its common name is 'vegetal insulin'. However, there have been practically no attempts so far to determine scientifically whether it has antidiabetic effects and we decided to administer leaf decoctions, over extended periods, to normal and streptozotocin-diabetic rats, and investigate the effects of this treatment on the physiological and metabolic parameters that are altered in diabetic animals. The experimental model adopted was shown to be appropriate by running a parallel treatment with insulin, which led to expected improvements in several abnormal parameter values. The decoction treatment significantly reduced the intake of both food and fluid and the volume of urine excreted, as well as the levels of blood glucose, urinary glucose and urinary urea, in comparison with controls. Lipid metabolism was not affected by the treatment; nor was the level of hepatic glycogen in diabetic animals, which indicated that the mechanism responsible for the improvement in carbohydrate metabolism, observed in animals treated with the decoction, could not involve inhibition of glycogenolysis and/or stimulation of glycogenesis. The fact that normal animals treated with C. sicyoides exhibited no changes in any of the measured parameters suggests that its mode of action in diabetic animals does not resemble those of sulphonylurea or insulin. It may, however, act in a similar way to biguanide, via inhibition of gluconeogenesis.

Increased glucose synthesis in renal tubule fragments from hyperthyroid rats

Rates of glucose synthesis from several substrates were examined in renal tubule fragments from hyperthyroid rats. A hyperthyroid state was induced by daily intraperitoneal injections of thyroxine (T-4) (100 mu g/100 g body weight) for 14 days. At the end of the experimental period, plasma triiodothyronine and T-4 levels were six and eight times higher, respectively, than initial values. Hyperthyroid rats gained less weight and had lower blood glucose despite an increased food intake. In both control and hyperthyroid rats, rates of glucose production by renal tubule fragments were higher with glutamine and glycerol than with lactate, alanine, or glutamate. T-4 treatment induced a significant increase in the de novo glucose synthesis from all substrates, except glutamine. The highest percent increase was obtained with alanine (64%), compared with 31-40% for glutamate, lactate, and glycerol. The T-4 treatment induced increase in glucose synthesis by renal tubule fragments suggests that renal gluconeogenesis contributes to enhance glucose production in hyperthyroidism.

Metabolic changes in Brycon cephalus (Teleostei, Characidae) during post-feeding and fasting

Metabolic changes during the transition from post-feeding to fasting were studied in Brycon cephalus, an omnivorous teleost from the Amazon Basin in Brazil. Body weight and somatic indices (liver and digestive tract), glycogen and glucose content in liver and muscle, as well as plasma glucose, free fatty acids (FFA), insulin and glucagon levels of B. cephalus, were measured at 0, 12, 24, 48, 72, 120, 168 and 336 h after the last feeding. At time 0 h (the moment of food administration, 09.00 h) plasma levels of insulin and glucagon were already high, and relatively high values were maintained until 24 h post-feeding. Glycemia was 6.42 +/- 0.82 mM immediately after food ingestion and 7.53 +/- 1.12 MM at 12 h. Simultaneously, a postprandial replenishment of liver and muscle glycogen reserves was observed. Subsequently, a sharp decrease of plasma insulin occurred, from 7.19 +/- 0.83 ng/ml at 24 h of fasting to 5.27 +/- 0.58 ng/ml at 48 h. This decrease coincided with the drop in liver glucose and liver glycogen, which reached the lowest value at 72 h of fasting (328.56 +/- 192.13 and 70.33 +/- 14.13 mumol/g, respectively). Liver glucose increased after 120 h and reached a peak 168 h post-feeding, which suggests that hepatic gluconeogenesis is occurring. Plasma FFA levels were low after 120 and 168 h and increased again at 336 h of fasting. During the transition from post-feeding to fast condition in B. cephalus, the balance between circulating insulin and glucagon quickly adjust its metabolism to the ingestion or deprivation of food. (C) 2002 Elsevier B.V. All rights reserved.

Seasonal metabolic depression, substrate utilisation and changes in scaling patterns during the first year cycle of tegu lizards (Tupinambis merianae)

The tegus increase in body mass after hatching until early autumn, when the energy intake becomes gradually reduced. Resting rates of oxygen consumption in winter drop to 20% of the values in the active season (Vo(2)=0.0636 ml g(-1) h(-1)) and are nearly temperature insensitive over the range of 17-25degreesC (Q(10)=1.55). During dormancy, plasma glucose levels are 60% lower than those in active animals, while total protein, total lipids and beta-hydroxybutyrate are elevated by 24%, 43% and 113%, respectively. In addition, a significant depletion of liver carbohydrate (50%) and of fat deposited in the visceral fat bodies (24%) and in the tail (25%) and a slight loss of skeletal muscle protein (14%) were measured halfway through the inactive period. Otherwise, glycogen content is increased 4-fold in the brain and 2.3-fold in the heart of dormant lizards, declining by the onset of arousal. During early arousal, the young tegus are still anorexic, although Vo(2) is significantly greater than winter rates. The fat deposits analysed are further reduced (62% and 45%, respectively) and there is a large decrease in tail muscle protein (50%) together with a significant increase in glycogen (2-3-fold) and an increase in plasma glucose (40%), which suggests a role for gluconeogenesis as a supplementary energy source in arousing animals. No change is detectable in citrate synthase activity, but beta-hydroxyacyl CoA dehydrogenase activities are strongly affected by season, reaching a Mold and 5-fold increase in the liver tissue of winter and arousing animals, respectively, and becoming reduced by half in skeletal muscle and heart of winter animals compared with late fall or spring active individuals. From hatching to late autumn, the increase of the fat body mass relatively to body mass is disproportionate (b=1.44), and the mass exponent changes significantly to close to 1.0 during the fasting period. The concomitant shift in the Vo(2) mass exponent in early autumn (b=0.75) to values significantly greater than 1.0 in late autumn and during winter dormancy indicates an allometric effect on the degree of metabolic depression related to the size of the fat stores and suggests greater energy conservation in the smaller young.

Effect of fasting on carbohydrate metabolism in frugivorous bats (Artibeus lituratus and Artibeus jamaicensis)

The compensatory changes of carbohydrate metabolism induced by fasting were investigated in frugivorous bats, Artibeus lituratus and Artibeus jamaicensis. For this purpose, plasma levels of glucose and lactate, liver and muscle glycogen content, rates of liver gluconeogenesis and the activity of related enzymes were determined in male bats. After a decrease during the first 48 h of fasting, plasma glucose levels remained constant until the end of the experimental period. Plasma lactate levels, extremely high in fed bats, decreased after 48 h of fasting. Similarly, liver glycogen content, markedly high in fed animals, was reduced to low levels after 24 h without food. Muscle glycogen was also reduced in fasted bats. The expected increase in liver gluconeogenesis during fasting was observed after 48 h of fasting. The activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase were not affected by food withdrawn. on the other hand, fasting for 24 h induced an increase in the activity of liver cytosolic phosphoenolpyruvate carboxykinase. The data indicate that liver gluconeogenesis has an important role in the glucose homeostasis in frugivorous bats during prolonged periods of food deprivation. During short periods of fasting liver glycogenolysis seems to be the main responsible for the maintenance of glycemia. (C) 2005 Elsevier B.V. All rights reserved.

Effects of monocrotaline on energy metabolism in the rat liver

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frutose em humanos: Efeitos metabólicos, utilização clínica e erros inatos associados

This article reviews the metabolism of fructose and sorbitol, their main clinical indications and the consequences of inadequate use. Fructose, an important carbohydrate in the diet, is present mostly in fruits and vegetables; it can also be synthesized from glucose in the organism, through the sorbitol. Fructose is known for its metabolism's inherent errors, whose clinical manifestations are potentially serious, as well as for its use as a glucose substitute in the diabetic patients' diet, due to its metabolism not being dependent from insulin. In the last years, especially in developed countries, the consumption of fructose has increased considerably, due to its use as a sweetener in industrialized foods. However, adverse side-effects may occur with the excessive ingestion of fructose, such as the increase in blood's triglycerides and cholesterol. Therefore, to know which are the patients' normal blood levels is quite important for establishing the safe amount of fructose to be prescribed, as well as for allowing the screening of metabolism diseases associated with fructose.