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H J Seitz

Publications and source records attributed to H J Seitz.

At least 73 records · Page 4Linked to original sources
PubMed1981

Effect of different thyroid states on rat liver glucokinase synthesis and degradation in vivo.

The role of different thyroid states on the rate of rat liver glucokinase synthesis and degradation was studied in vivo by the radioimmunochemical technique. In eu- and hyperthyroid starved rats, glucose refeeding induced a rapid and similar increase in glucokiase synthesis and activity, whereas in hypothyroid rats, only minor alterations in synthesis and activity was observed. 3,3',5'-Triiodo-L-thyronine substitution in hypothyroid animals restored the response of the enzyme within 24 h. The thyroid states per se had only a minor effect on glucokinase synthesis during the starvation period. In addition, in hypo-, eu-, and hyperthyroid rats adapted to a glucose diet, glucokinase degradation was estimated by double-pulse-labeling experiments, applying [14C]- and [3H]leucine. From the 3H/14C ratios, similar apparent half-lives were calculated: 17-19 h. It is concluded that thyroid hormones in their physiological range are an essential factor in the induction of hepatic glucokinase in vivo, exerting their action probably via a "permissive" effect, yet the degradation rate is unaffected by the thyroid state.

Animals↗
PubMed1981

Rapid rise in plasma glucagon induced by acute cold exposure in man and rat.

The effect of acute cold exposure on the concentration of glucagon in the blood was investigated in man and in intact and adrenalectomized rats. In man fasted overnight acute cold exposure, which caused a twofold increase in O2-consumption resulted in a rapid rise in plasma glucagon. The levels of insulin and blood glucose remained unaltered, while the concentration of serum free fatty acids and beta-hydroxybutyrate increased. In fasted intact rats acute cold exposure lead to similar effects. A close parallelism between the rise in plasma glucagon and the concentration of hepatic cycloAMP was observed. Adrenalectomy did not impair the cold induced rise in plasma glucagon and hepatic cycloAMP. It is concluded that acute cold exposure caused a rapid rise in the concentration of plasma glucagon leading to an increase in the concentration of hepatic cycloAMP, thus enhancing the rate of hepatic gluconeogenesis and ketogenesis. As these alterations were similar in the absence of glucocorticoids and medulla-derived catecholamines, it is suggested that glucagon may play a role in the metabolic adaptation to acute cold exposure.

Adult↗
PubMed1981

Starvation-induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo.

The role of thyroid hormones in the metabolic adaptation to starvation was investigated in vivo. Glucose production, measured by tracer technique, was enhanced in hyperthyroid (185%) and reduced in hypothyroid (39%) 48-hour starved rats (euthyroid control = 100%). Urinary nitrogen excretion was increased in hyperthyroidism (132%) and decreased in hypothyroidism (70%). Compared with euthyroid controls (=100%) significant alterations for the following regulatory parameters of hepatic gluconeogenesis were observed: 1) tissue cAMP (124%/91%) and protein kinase activation (132%/90%), with a corresponding crossover between pyruvate and P-enolpyruvate (-/+/+/-); 2) pyruvate carboxylase (165%/60%), P-enolpyruvate carboxykinase (140%/82%) and fructose-1.6-bis-P-phosphatase activity (99%/61%), and 3) tissue content of the glucogenic amino acids: alanine (187%/66%) and glutamate (187%/88%), aspartate (179%/68%) and glutamate (137%/75%), as well as of oxaloacetate (254%/66%) and malate (164%/104%). The observed alterations in hepatic oligomycine-sensitive oxygen consumption in hyper- (161%) and hypothyroidism (51%) were related to the measured concentration of the intermediates of the citric acid cycle, the energy state and the mitochondrial redox state. In summary, the different rates of hepatic glucose production in hyper- and hypothyroid starved rats observed in vivo can be ascribed to 1) cAMP content, 2) gluconeogenic key enzyme activities, 3) glucogenic precursor supply and 4) cofactor (ATP) availability.

Animals↗
PubMed1980

Regulation of hepatic phosphoenolpyruvate carboxykinase (GTP). Role of dietary proteins and amino acids in vivo and in the isolated perfused rat liver.

The effect of protein feeding and the addition of amino acids on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP : oxalacetate carboxylyase (transphosphorylating), EC 4.1.1.32) was investigated in vivo and in the isolated perfused rat liver. Protein feeding resulted in a considerable increase in phosphoenolpyruvate carboxykinase activity within 6 h. This rise was independent of the presence of glucocorticoids. In the isolated perfused liver system amino acids per se had a small effect on phosphoenolpyruvate carboxykinase activity and led to an increase by 20% when glucocorticoids were present, but resulted in a rise by 100% when glucocorticoids plus dibutyryl cyclic AMP were added to the perfusion medium. The effect of amino acids in the presence of dibutyryl cyclic AMP could also be observed in the liver of glucocorticoid-deprived rats. Cycloheximide, a translational inhibitor, totally blocked all effects of amino acids on enzyme activity. These results indicate that the concentration of amino acids in the portal vein modify the regulation of phosphoenolpyruvate carboxykinase by cyclic AMP.

Amino Acids↗
PubMed1980

In vivo glucose turnover in hypo- and hyperthyroid starved rat.

The effect of hypo- and hyperthyroidism on glucose turnover in vivo was determined in unanesthetized rats starved for 48 h. Glucose pool and decay rate of specific radioactivity of blood glucose was measured after bolus injection of a mixture of 3H-(2)- and 14C-(U)-glucose under steady state conditions. Compared with euthyroid controls (= 100%), hypothyroidism resulted in a decrease of blood glucose concentration (81%), glucose pool (52%), glucose disappearance rate (39%), and total glucose recycling (12%). In contrast, hyperthyroidism led to an increase of blood glucose concentration (148%), glucose pool (121%), glucose disappearance rate (185%), and total glucose recycling (163%). T 1/2 for glucose was calculated to be 46 min in the hypo-, 34 min in the eu-, and 22 min in the hyperthyroid state. The concentration of circulating glucoregulatory hormones, corticosterone and glucagon were elevated in hyperthyroid rats, while glucagon was diminished in hypothyroid animals. No difference in the level of insulin was found. These data demonstrate that glucose turnover in vivo is a function of the thyroid state being reduced in hypo- and considerably increased in hyperthyroidism.

Animals↗
PubMed1980

Dietary control of circadian variations in serum insulin, glucagon and hepatic cyclic AMP.

The effect of a high-protein diet (favoring hepatic glucose production) and of a high-carbohydrate diet (favoring glucose utilization) on the concentration of insulin and glucagon in the blood and on adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the liver was investigated during a 24-hour cycle in rats. Feeding a high-protein diet resulted within 3 hours in an increase in the concentration of insulin (+100%) and glucagon (+220%). Whereas feeding a high-carbohydrate diet again induced a rise in insulin (+140%), no alterations in glucagon were observed. Hepatic cyclic AMP oscillated up or down under the protein or carbohydrate diet, respectively. A correlation between the insulin/glucagon molar ratio and the concentration of hepatic cyclic AMP was found. Protein-bound cyclic AMP, an indicator of protein kinase activation, corresponded closely to total cyclic AMP tissue concentration. The activity of a gluconeogenic key enzyme, P-enolpyruvate carboxykinase oscillated in parallel to hepatic cyclic AMP. Our data demonstrate that the protein and carbohydrate content of the diet determines the shape of circadian variation of hepatic cyclic AMP, insulin and glucagon.

Animals↗
PubMed1980

Hepatic glucokinase turnover in intact and adrenalectomized rats in vivo.

Regulation of synthesis and degradation of glucokinase, key enzyme of glucose metabolism in liver, was investigated in intact and adrenalectomized rats in vivo, using pulse-labeling experiments and a specific antibody against the enzyme. Refeeding glucose in starved rats resulted in a marked rise in glucokinase activity (from the starvation value 4.8 mU/mg protein to 9.6 mU/mg protein at 4 h, and to 21.8 mU/mg protein at 8 h), which closely correlated to the increase in enzyme synthesis by factor 1.7 at 4 h and 4.1 at 8 h. Similar alterations in enzyme activity and synthesis were observed after glucose refeeding in adrenalectomized/glucocorticoid-restored rats. In contrast, refeeding glucose in adrenalectomized rats led within 8 h only to a small elevation in enzyme activity (from the starvation value 4.2 mU/mg protein to 9.6 mU/mg protein) and a minor rise in enzyme synthesis (factor 1.7). Glucocorticoids per se were without effect on glucokinase activity and synthesis in starved rats. When adapted to pure glucose diet, intact, adrenalectomized and adrenalectomized/glucocorticoid-restored rats showed highly elevated levels in glucokinase (27, 23, 28 mU/mg protein, respectively). However, enzyme synthesis was elevated significantly only in intact and adrenalectomized/glucocorticoid-restored rats. Under these conditions glucokinase degradation was estimated by the double-pulse-labeling technique, applying [14C]leucine and [3H]leucine. From the 3H/14C ratios the apparent half-lives were calculated: 17 h in intact and adrenalectomized/glucocorticoid-restored rats, and 35 h in adrenalectomized rats. It is concluded that in vivo glucocorticoids not only exert a 'permissive' action on glucokinase induction, but also enhance the degradation of the enzyme.

Adrenalectomy↗
PubMed1977

Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism.

The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation.

Animals↗
PubMed1976

Interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP) in the isolated perfused rat liver. Effects of cordycepin and cycloheximide.

The mechanism of the interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP: oxalocetate carboxylase, transphosphorylating, EC 4.1.1.32) was investigated in the isolated perfused rat liver using inhibitors of transcription or translation. Dibutyryl cyclic AMP produced a rapid increase in P-enolpyruvate carboxykinase activity. The response of the enzyme to the cyclic nucleotide ceased however, at 4 h, but was restored by dexamethasone. The dibutyryl cyclic AMP-induced increase in P-enolpyruvate carboxykinase activity was completely blocked by cycloheximide, but not not by cordycepin. However, cordycepin totalaly suppressed the "permissive" effect of dexamethasone on the response of the enzyme to dibutyryl cyclic AMP. Preperfusion of the livers with dexamethasone and cycloheximide, following by perfusion without the steroid hormone and the inhibitor, resulted in a rapid rise in P-enolpyruvate carbosykinase activity, which was not affect by cordycepin. If livers were preperfused with cordycepin for different time-periods, followed by dibutyryl cyclic AMP stimulation of P-enolpyruvate carboxykinase synthesis, the response of the enzyme to the cyclic nucleotide was progressively reduced, achieving 50% inhibition after 1.5 h of preperfusion. These results suggest that the induction of hepatic P-enolpyruvate carboxykinase to maximum values, brought about by cyclic AMP at the level of translation, depends on the supply of newly synthetized mRNA provided by the transcriptional action of glucocorticoids.

Animals↗
PubMed1976

Effect of cold exposure on phosphoenolpyruvate carboxykinase (GTP) activity and cyclic amp concentration in livers of starved rats. Role of glucorticoids.

The effect of cold exposure (5 degrees C) on the concentration of cyclic AMP and on the activity of phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) was investigated in the liver of intact and adrenalectomized starved rats. Intact starved rats responded to cold exposure with a large increase in both the concentration of hepatic cyclic AMP and the activity of phosphoenolpyruvate carboxykinase above the starvation level. Adrenalectomy did not impair the cold-induced maximum elevation of cyclic AMP but totally prevented the response of the enzyme to cold. Yet, this response was completely restored by hydrocortisone treatment, while the steroid per se had no effect on enzyme activity. In isolated perfused livers of intact starved rats dibutyryl cyclic AMP provoked an immediate dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level even if mRNA synthesis was inhibited by cordycepin. However, cyclic AMP was ineffective in increasing enzyme activity in livers of adrenalectomized rats. From these results it is suggested (i) that in starved rats the adaptation to the enhanced glucose demand provoked by cold exposure includes the induction of hepatic phosphoenolpyruvate carboxykinase above the starvation level, (ii) that this induction is due to the cold-induced increase in hepatic cyclic AMP levels, (iii) that cyclic AMP stimulates enzyme synthesis at a post-transcriptional step and (iv) that the cold-induced cyclic AMP-mediated induction of phosphoenolpyruvate carboxykinase above the starvation level requires the "permissive" effect of glucocorticoids.

Adrenalectomy↗
PubMed1976

Induction of rat liver phosphoenolpyruvate carbonxykinase (GTP) by cyclic AMP during starvation. The permissive action of glucocorticoids.

The effect of starvation on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32), and on the response of the enzyme to N6-O2'dibutyryl adenosine 3', 5'-monophosphate was investigated in intact and glucocorticoid-deprived rats. In the liver of intact animals, starvation produced a rapid increase in the concentration of cyclic AMP and a corresponding increase in the activity of phosphoenolpyruvate carboxykinase. The kinetics of both changes were not affected by adrenalectomy. Injection of N6-O2'-dibutyryl adenosine 3', 5'-monophosphate into intact starved rats resulted in an immediate, dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level. Adrenalectomy completely blocked the response of the enzyme to the cyclic nucleotide. Restoration of hydrocortisone to the adrenalectomized animals restored the full N6-I2'dibutyryl adenosine 3', 5'-monophosphate effect after a lag period of 2 h. The physiological significance of these findings is considered. The data are interpreted with regard to the current hypothesis that glucocorticoids promote an increase in translatable phosphoenolpyruvate carboxykinase mRNA, while cyclic AMP enhances the translation of preexisting specific mRNA templates.

Adrenalectomy↗
PubMed1976

Physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis during starvation in rats.

The physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis was investigated during a 48-hr starvation period by studying the factors presumed to control the rate of glucose synthesis in the final gluconeogenetic pathway. Rats were used, in which glucorticoids were removed by adrenalectomy before starvation, and in which serum insulin was kept constant before and after food withdrawal by pre-feeding with a proteinfree diet. It was found that adrenalectomized rats at constantly low serum insulin levels responded to starvation as rapidly, and to the same degree, as intact control subjects (1) by a significant increase in plasma glucagon and, consequently, in hepatic cAMP concentration; (2) by a coordinate elevation of the activities of hepatic pyruvate carboxylase, P-enolpyruvate carboxykinase, and fructose-1,6-diphosphatase; (3) by systematic alterations in the concentration of effectors of gluconeogenetic key enzymes; (4) by a shifting of the cytoplasmic NAD system towards the reduced state; (5) by a decrease in the intrahepatic concentration of glycogenic precursor substrates. These results suggest that the hepatic gluconeogenic response to starvation with respect to the regulatory factors 1-5 occurs independently from changes in the concentration of plasma glucocorticoids and insulin. The crossing over of the gluconeogenetic intermediates between pyruvate and P-enolpyruvate (PEP), which was observed in intact but not in adrenalectomized rats, supports the assumption that during starvation, glucocorticoids enhance the rate of glucose production by the liver predominantly by permitting hepatic cAMP to stimulate the yet undefined mechanism, which has been demonstrated in the isolated perfused rat liver to control the substrate flow between pyruvate and PEP.

Adenine Nucleotides↗
PubMed1976

Concentration of cyclic AMP in rat liver as a function of the insulin/glucagon ratio in blood under standardized physiological conditions.

The concentration of insulin and glucagon in peripheral blood and the concentration of cAMP in liver was followed in rats throughout a 48 hour starvation period and up to 6 hours afer refeeding glucose or casein. By so changing the insulin/glucagon molar ratio from minimum to maximum values, simultaneous inverse changes in the concentration of hepatic cAMP could be induced. The study, thus, suggests that during a starvation-refeeding cycle the level of cAMP in the liver is regulated predominantly by the insulin/glucagon ratio in the blood. Possible criticisms of this conclusion are discussed.

Adrenalectomy↗