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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.

Intravenous (IV) administration of angiotensin II (0.95 nmol/100 g body weight) produced a marked increase in plasma glucose of 20 h fasted rats. To investigate the possibility of a stimulation of gluconeogenesis, conscious unrestrained rats were continuously infused with [14C]bicarbonate, 60 microl/min (0.18 microCi/min), and label incorporation into circulating glucose was determined before and after angiotensin injection. The rate of 14C incorporation into blood glucose of fed rats increased significantly after angiotensin II administration, a 279% increase after 20 min (P < 0.01). In conclusion, the results of the present study show that the hyperglycemia induced by intravenous (IV) administration of angiotensin II is accompanied by an activation of gluconeogenesis, as evidenced by a rapid and marked increase in the rate of 14CO2 incorporation into circulating glucose.

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 H14CO-3 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 [6-3H]-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.

Microinjections of carbachol (50 nmol) or neostigmine (25 nmol) in 0.5 ml saline into the ventromedial nucleus of the hypothalamus (VMH) (but not into the lateral hypothalamic area) of fed, conscious rats produced marked increases in plasma glucose and lactate, which were suppressed or markedly reduced by previous adrenodemedullation. The rate of incorporation of 14C from infused bicarbonate (0.60 microliter, 0.20 microCi/min), an index of gluconeogenic activity, increased significantly after VMH administration of neostigmine. The data suggest that cholinergic synapses in the VMH participate of a central glucoregulatory system that increases hepatic glucose production mainly through a stimulation of adrenal medulla epinephrine secretion.

Intracerebroventricular administration of carbachol (27 nmol in 5 microliters 0.15 M NaCl) produced marked hyperglycemia in 24-h fasted rats, despite the negligible amounts of preformed liver glycosyl residues. To investigate the possibility of a stimulation of gluconeogenesis, conscious unrestrained rats were continuously infused with [14C]bicarbonate (0.51 microliters, 0.18 muCi/min) and label incorporation into circulating glucose determined before and after intraventricular injection. The rate of 14C incorporation into blood glucose of fed rats was not affected by intraventricular injection of 0.15 M NaCl but increased significantly after carbachol administration. In both fed and 24-h fasted rats the hyperglycemia induced by intraventricular carbachol was accompanied by marked increases in plasma lactate. Previous adrenodemedullation prevented both the hyperglycemia and the hyperlactemia. Liver pyruvate kinase activity was reduced in carbachol-treated rats, when the enzyme was assayed with suboptimal concentrations of phosphoenolpyruvate and in the absence of fructose 1,6-biphosphate. Phosphoenolpyruvate carboxykinase activity was not affected. The data suggest that central chemical stimulation with cholinergic agents induces a rapid activation of liver gluconeogenesis, which probably results from an increased sympathetic outflow for epinephrine secretion by the adrenal medulla.

1. The effect of adrenalectomy on the adjustments of carbohydrate metabolism to fasting was studied in rats fed a high-protein, carbohydrate-free (HP) diet. 2. Fasting for 24 h induced a 20% decrease of blood glucose levels in intact rats on the balanced, control (C) diet, but did not affect the blood glucose levels of rats adapted to the HP diet. After adrenalectomy, HP rats lost their capacity to maintain constant blood glucose levels during fasting, but the reduction in blood glucose (30% after 24 h) took longer to appear and was 50% smaller than in adrenalectomized C-rats. 3. Intact rats on the control diet responded to fasting with increased in vitro hepatic gluconeogenic capacity as well as increased phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase activities. Adrenalectomized C-rats also responded to fasting with increased gluconeogenesis and PEPCK activity. In contrast, for both intact and adrenalectomized HP-fed rats, liver gluconeogenesis and PEPCK activity, which were already high in the fed state, did not change or even decreased slightly after fasting. 4. After food restriction, the rates of glucose replacement by adrenalectomized rats on the control diet were higher than those of intact animals on the same diet. This effect was not observed in HP-fed rats, in which the rates of glucose replacement were even slightly lower in adrenalectomized than in intact animals. 5. These data suggest that the mechanism of fasting-induced hypoglycemia after adrenal removal is different for HP and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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.