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H J Seitz

Publications and source records attributed to H J Seitz.

At least 55 records · Page 3Linked to original sources
PubMed1984

Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism.

Despite their enhanced endogenous de novo cholesterol synthesis, hyperthyroid patients exhibit decreased total and low-density lipoprotein (LDL) cholesterol levels in the serum because of a concomitant increase in LDL catabolism, cholesterol excretion by bile and a reduced enterohepatic bile acid circulation. Hypothyroidism exhibits a reduction (1) in the synthesis of cholesterol and (2) in LDL catabolism, whereas cholesterol reabsorption is unchanged or even enhanced. In addition, obese hypothyroid patients showed an increased cholesterol synthesis which is independent of thyroid hormones and which contributes to the observed LDL cholesterolaemia. Thyroid hormones per se have only a minor influence on plasma triglyceride (TG) levels, but they induce an acceleration of TG turnover and chylomicron clearance rate. In addition, the hepatic lipogenic capacity is increased in hyperthyroidism and reduced in hypothyroidism. However, hepatic total and very low-density lipoprotein (VLDL) triglyceride output is decreased by thyroid hormones due to a reduced re-esterification and a simultaneously increased oxidation of newly synthesized fatty acids. Hypothyroid livers, by contrast, reveal an increased VLDL secretion. Despite their reduced lipogenesis, obese hypothyroidism is often accompanied by a hypertriglyceridaemia type III. The simultaneous stimulation of the synthesis of fatty acids, which are still in part converted to TG, and the degradation of TG contributes to the enhanced thermogenesis in hyperthyroid patients. The concentration and turnover of free fatty acids (FFA) are increased in hyperthyroidism, resulting from a thyroid hormone-induced increase in: (1) lipolysis, explained by an increased adipose tissue sensitivity for lipolytic hormones; and (2) oxidation of fatty acids to CO2 as well as to ketone bodies (KB).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed1984

Rapid action of insulin and cyclic AMP in the regulation of functional messenger RNA coding for glucokinase in rat liver.

The mRNA activity coding for rat liver glucokinase was measured in vivo under different hormonal and nutritional conditions. Starvation resulted in minimal levels of glucokinase mRNA activity. Glucose refeeding caused a 4-fold induction of glucokinase mRNA within 48 h, which followed similar alterations in enzyme activity. Minimal values for glucokinase mRNA were also measured in diabetic animals fed glucose and were significantly elevated by insulin injection within 1.5 h. Administration of dibutyryl cyclic AMP to glucose-fed rats caused a rapid loss of the specific mRNA. The half-life of glucokinase mRNA, determined after the administration of cordycepin to glucose-fed animals, was approximately 40 min. This half-life was unaffected by the administration of dibutyryl cyclic AMP. Glucokinase mRNA was reduced 60% in glucose-fed adrenalectomized or thyroidectomized rats. The activity of the glucokinase mRNA agreed well with the measured rates of enzyme synthesis. These data indicate that insulin regulates hepatic glucokinase synthesis in vivo by increasing glucokinase mRNA; its effect is reduced by the absence of glucocorticoids or thyroid hormones and is rapidly antagonized by cyclic AMP.

Animals↗
PubMed1984

Thyroid hormone action on intermediary metabolism. Part I: respiration, thermogenesis and carbohydrate metabolism.

The effect of thyroid hormones on mitochondrial respiration are summarized: T3 directly stimulates mitochondrial respiration and the synthesis of adenosine 5'-triphosphate (ATP). Cytosolic ATP availability is increased by a thyroid hormone-induced increase in adenine nucleotide translocation across the mitochondrial membrane; the steady state ATP concentration and the cytosolic ATP/adenosine 5'-diphosphate (ADP) ratio is even decreased in hyperthyroid tissues because of the simultaneous stimulation of the synthesis and consumption of ATP. With regard to the thyroid hormone-induced energy wasting processes, heart work, intra- and interorgan futile cycling and Na+/K+-ATPase are involved to varying degrees. As a consequence of the thyroid hormone-induced hydrolysis of ATP, thermogenesis is increased in hyper- and decreased in hypothyroidism. Despite an increased rate of glucose utilization, clinical and experimental hyperthyroidism is often characterized by an abnormal oral glucose tolerance test. This finding is due to the thyroid hormone-induced increase in intestinal glucose absorption as well as the still enhanced endogenous glucose production in the liver. Hypothyroid patients show a reduced glucose tolerance test because of a decrease in intestinal glucose absorption and a sometimes reduced glucose turnover. The thyroid hormone-induced alterations in glucose metabolism are most probably not due to alterations in serum insulin levels and/or to a peripheral insulin resistance at the receptor level.

Adenosine Triphosphate↗
PubMed1984

Effect of ketone bodies on glucose production and utilization in the miniature pig.

The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-beta-OH-butyrate (Na-DL-beta-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, alpha-amino-N, and free fatty acids (FFA) were all reduced. Infusion of Na-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and alpha-amino-N increased. Infusing different amounts of Na-DL-beta-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed. Prevention of the Na-DL-beta-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 mumol/kg X min) did not prevent hypoglycemia. Infusion of Na-DL-beta-OHB plus insulin (0.4 mU/kg X min) showed no additive effect on the inhibition of Ra. Ketones did not inhibit the insulin-stimulated metabolic clearance rate (MCR) for glucose. Infusion of somatostatin (0.2 micrograms/kg X min) initially decreased plasma glucose, Ra, and Rd, which was followed by an increase in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-beta-OHB, hypoglycemia and the reduced Ra were maintained. In the anaesthetized 24-h starved miniature pig, Na-DL-beta-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and alpha-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, alpha-amino-N, and FFA were decreased, while ketone body utilization increased. Repeated infusion of Na-DL-beta-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary N-excretion accelerated. To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone body-induced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in R(a), glucose utilization declines during ketone infusion. (d)The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

3-Hydroxybutyric Acid↗
PubMed1983

Glucose production measured by tracer and balance data in conscious miniature pig.

The rate of glucose production was estimated in the conscious, unrestrained miniature pig during metabolic adaptation to starvation (up to 120 h) by the simultaneous use of three different techniques: 1) the isotopedilution technique, 2) the arteriohepatovenous catheter technique, and 3) the urinary nitrogen balance. During the experimental period 1) whole-body glucose turnover decreased, whereas the amount of glucose recycling increased; 2) splanchnic glucose output decreased, whereas the rate of splanchnic precursor extraction increased up to 48 h, followed by a decrease; 3) gut glucose consumption amounted to about 30% of splanchnic glucose output; and 4) urinary nitrogen excretion declined continuously. The comparison of the different methods revealed that during starvation 1) tracer-determined glucose production rate was within the range (+/- 10%) of the splanchnic glucose output; 2) mean hepatic glucose output overestimated the tracer data by about 30-40%; 3) splanchnic glucose output underestimated hepatic glucose production by the amount of gut glucose consumption; 4) tracer-determined glucose recycling corrected for isotope dilution and amino acid contribution was within the range of splanchnic gluconeogenic precursor extractions. Considering the limitations (e.g., gut glucose consumption, gut lactate and alanine release, blood flow measurement) and methodological problems of the different approaches applied, it is evident that each method reflects different events. It is suggested that the versatile tracer technique combined with nitrogen balance should be preferred for measurement of endogenous glucose production.

Alanine Transaminase↗
PubMed1983

Thyroid hormone regulation of glucose homeostasis in the miniature pig.

The effect of different thyroid states on glucose homeostasis was investigated during metabolic adaptation to starvation in the conscious unrestrained miniature pig. Moderate hyperthyroidism increased the rate of glucose turnover, whereas hypothyroidism was without effect. Glucose recycling was elevated in hyperthyroid pigs, and reduced after thyroidectomy. Supplementary doses of T4 normalized total glucose recycling. Glucose metabolic clearance rate and pool size were unaffected by thyroid hormones. During starvation serum insulin showed a similar decrease in all thyroid states; glucagon increased in euthyroid and hypothyroid pigs, although it was already elevated in the hyperthyroid fed state. Serum cortisol levels although varying were enhanced in hyperthyroid and hypothyroid-T4-treated pigs. Glucogenic precursor concentration and cumulative urinary N-excretion were increased in hyperthyroid pigs. It is concluded that 1) even a moderate hyperthyroidism produces an increase in glucose turnover and a concomitant acceleration in protein breakdown, and 2) thyroid hormone is essential for the starvation-induced total glucose recycling.

Animals↗
PubMed1983

Clinical value of free-thyroxin measurements.

Although discrepancies have been reported between free thyroxin (fT4) in serum and actual thyrometabolic status, the concentration of free thyroid hormones in blood is thought to be an important determinant of the thyrometabolic status of patients. Therefore, the diagnostic value of fT4 measurement has been emphasized. This prompted us to evaluate the diagnostic significance of direct fT4 measurement. We conclude that: (a) The different fT4 radioimmunoassays we examined did not excel the total thyroxin, fT4 index, or thyroxin/thyroxin-binding globulin ratio in the laboratory assessment of thyroid status and alterations in thyroid hormone-thyroxin-binding globulin relationships. (b) The fT4 values obtained by direct or indirect methods always shifted in parallel to total thyroxin with respect to borderline increased or decreased total thyroxin, subclinical hypothyroidism, isolated hypertriiodothyroninemia, and thyroxin substitution.

Humans↗
PubMed1983

Alteration in thyroid hormone concentration during and after coronary bypass operation.

The effect of a surgical stress on serum TSH, T4, free T4, T3, rT3 and TBG was measured before, during and after a coronary bypass operation. Precautions were taken to age, sex, pre-operative nutritional state, anamnestic illness, pre- and post-operative medication. Compared to the pre-operative period TSH increased during operation and normalized at the first post-operative day, while only minor alterations for total and free serum T4 were observed. T3 and rT3 declined at the start of extracorporal circulation, T3 remained reduced during the post-operative period, while rT3 reached its pre-operative value at the first post-operative day. It is concluded that the coronary bypass operation evokes a rapid decline in T3, which is not normalized by the TSH induced response of the thyroid gland, while the post-operative period is characterized by a "low T3 state". The clinical relevance of this finding is discussed with respect to the cardiovascular and the nutritional state of the patients in the post-operative period.

Adult↗
PubMed1982

Renal phosphoenolpyruvate carboxykinase turnover in hypo- and hyperthyroid rat in vivo.

The effect of hypo- and hyperthyroidism on activity, synthesis and degradation of renal cytosolic phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was studied in the rat by radioimmunological techniques. In hypo- and euthyroid rats, starvation induced similar alterations in enzyme activities and relative rates of synthesis, whereas in hyperthyroid rats the increase in both was significantly reduced. Substitution of L-thyroxine in hypothyroid rats resulted in a decrease in activity and synthesis within 18 h as observed in hyperthyroid animals. The apparent half-life of the enzyme measured by double-pulse labeling experiments was approx. 13 h in euthyroid animals. The rate of degradation was unaffected by the different thyroid states.

Animals↗
PubMed1982

pH-dependency of iodothyronine metabolism in isolated perfused rat liver.

1. Isolated livers from fed male rats were perfused for 2 h with T4 (L-thyroxine), T3 (L-3,3',5-tri-iodothyronine) or rT3 (L-3,3',5'-tri-iodothyronine) at different pH values (7.1--7.6) in a fully synthetic medium, whereby normal metabolic functions were maintained without addition of rat blood constituents or albumin. 2. T3 output into the medium and net T3 production reached a maximum at a pH of the medium of 7.2 and significantly decreased with alteration of the pH when livers were perfused with T4 as a substrate. 3. However, the net T4 and T3 uptake by the liver, as well as the hepatic T4 and T3 content after perfusion, were not dependent on the pH of the perfusion when livers were offered T4 or T3 as substrates respectively. 4. Determination of intracellular pH by the analysis of the distribution of the weak acid dimethyloxazolidinedione allows the conclusion that the pH optimum of iodothyronine 5'-deiodinase in the intact perfused liver corresponds to the maximum determined in vitro for the membrane-bound enzyme localized in the endoplasmic reticulum. 5. The rapid 5'-deiodination of rT3 to 3,3'-T2 (L-3,3'-di-iodothyronine), the fast disappearance of 3,3'-T2, and the fact that no net rT3 production from T4 could be detected, supports the hypothesis that in rat liver iodothyronine 5'-deiodinase activity seems to predominate over iodothyronine 5-deiodinase activity. 6. Thus the rat liver can be considered in normal physiological situations as an organ forming T3 from T4 and deiodinating rT3 originating from extrahepatic tissues, whereby the cellular iodothyronine 5'-deiodination rate is controlled by the intracellular pH.

Animals↗
PubMed1982

Starvation-induced ketone body production in the conscious unrestrained miniature pig.

The effects of short-term starvation (up to 5 days) on hepatic ketone body production was investigated in the conscious unrestrained miniature pig in vivo. Starvation induced an increase in arterial free fatty acid concentration (0.2-0.7 mM) with a concomitant elevation in hepatic free fatty acid extraction [-1.4-5.7 mumol/kg. minute),r = 0.53, P less than 0.005]. Ketone body production (sum of acetoacetate + beta-hydroxybutyrate) increased from 1.5 to 5.8 mumol/(kg . minute) in parallel (r = 0.71, P less than 0.0005). During starvation arterial insulin levels decreased, glucagon increased, cortisol remained unchanged and a "low T3 state' was observed. These data differ in some aspects from those reported for humans and dogs. Thus a species-specific variation in the fuel economy of the pig's body is proposed.

Animals↗
PubMed1982

Accelerated turnover of hepatic glucokinase in starved and streptozotocin-diabetic rat.

Rat liver glucokinase synthesis and degradation was estimated in fasted/fed and diabetic/diabetic-insulin-treated rats by the radioimmunological technique. Starvation and Streptozotocin-diabetes led to basal rates of synthesis and, consequently, to low levels in enzyme activity. In addition, a decrease in the apparent half-life from about 19 h in the fed or diabetic-insulin substituted to about 11 h in the starved or diabetic rat, respectively, was observed. Injection of Bt2cAMP into glucose-fed animals reduced glucokinase synthesis to basal levels within 90 min, without affecting enzyme activity. It is concluded that in metabolic states associated with elevated levels in tissue cAMP glucokinase synthesis is reduced to basal values and, in addition, its rate of degradation is significantly enhanced.

Animals↗
PubMed1982

3,5,3'-Triiodothyronine-induced synthesis of rat liver phosphoenolpyruvate carboxykinase.

Recent studies have indicated that the starvation induced increase in hepatic phosphoenolpyruvate carboxykinase (PEPck; EC 4.1.1.32) is accelerated in hyperthyroid animals, whereas enzyme degradation is unaffected by the thyroid state. Therefore, the present study was undertaken to investigate the possible direct effect of T3 on the synthesis of this important gluconeogenic regulatory enzyme in vivo and in the isolated perfused liver. T3 injection in hypothyroid animals stimulated PEPck synthesis within 6-12 h. The effect, being dose dependent and significant for 0.1 microgram T3/100 g BW, could be demonstrated in animals fasted or fed a carbohydrate-rich diet. Although varying in the basal rate of synthesis, the T3-induced increase in PEPck synthesis was similar in intact, thyroidectomized, adrenalectomized, and hypophysectomized animals. No additive effect with glucocorticoids was observed, suggesting that endogenous glucocorticoids are not necessary for the hormone action. The T3-induced effect on PEPck synthesis was not mediated by alterations in the endogenous cAMP level, as was indicated (1) by the different time course of PEPck induction via (Bu)2cAMP or T3, and 2) by the finding that T3 was effective also in diabetic animals, despite maximally enhanced tissue cAMP levels. In these animals insulin antagonized the T3 action on the enzyme. T3-mediated PEPck synthesis was not prevented by propranolol. Conversely, an additive effect with isoproterenol on enzyme activity was observed. T3 (1 nM) added to the isolated liver of hypothyroid rats perfused with the synthetic fluorocarbon medium supplemented with 10% iodothyronine free serum, stimulated incorporation of labeled leucine into PEPck protein within a 6-h perfusion time. Taken together, our data demonstrate that T3 at a physiological dose stimulates hepatic PEPck synthesis.

Adrenalectomy↗
PubMed1981

Effect of thyroid state on ketogenic capacity of the isolated perfused liver of starved rats.

The effect of different thyroid states on the oxidation of free fatty acids was investigated in the isolated perfused liver of 24-h-starved rats. 1. Compared with the euthyroid control the oxidation of oleate to ketone bodies as well as to CO2 was increased in hyper-, while it was unchanged in hypothyroid livers. 2. The addition of carnitine stimulated oleate oxidation in livers from eu- and hyperthyroid rats, but was without effect in hypothyroid livers. 3. Glucose did not affect the thyroid hormone-mediated effect of oleate conversion to ketone bodies. 4. Hepatic oxidation of octanoate was similar in all thyroid states. 5. Re-esterification of oleate was enhanced in hypo-, but reduced in hyperthyroidism. 6. The concentration of hepatic malonyl-CoA was decreased in hypo- and unchanged in hyperthyroid livers. 7. The concentration of cyclic AMP was elevated in the liver of hyperthyroid rats, no differences were observed between eu- and hypothyroid livers. However, increasing the hepatic cyclic AMP content by the addition of glucagon did not stimulate ketogenesis in eu- and hypothyroid livers. 8. The results indicate that thyroid hormones stimulate oleate oxidation by an accelerated transport of its CoA derivative into the mitochondrial compartment.

Adenine Nucleotides↗
PubMed1981

Mitochondrial and cytosolic ATP/ADP ratios in rat liver in vivo.

The ratio of ATP content/ADP content in livers from unanaesthetized fed rat was 0.9 in the mitochondrial matrix and 6.9 in the cytosol; the values for starved (48 h) animals were 1.0 and 5.9 respectively. The mitochondrial ratios observed in unanaesthetized animals were higher than in haemoglobin-free-perfused liver and lower than in isolated hepatocytes. Possible reasons for these differences may be related to oxygen supply and/or other factors. Further, data from anaesthetized rats with the liver exposed are given: mitochondrial ATP/ADP ratios were decreased with pentobarbital, but less so with ketamine as narcotic agent.

Adenosine Diphosphate↗