Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The survival and morphology of rat hepatocytes were examined in primary cell cultures that were maintained in serum-free medium supplemented with different hormones. Insulin and dexamethasone improved survival and maintenance of normal epithelial-shaped cells, although triiodothyronine did not alter cell survival or morphology when added to the medium alone or with other hormones. The level of mitochondrial alpha-glycerophosphate dehydrogenase and cytochromes a(+a3), b and c, but not c1, were increased in cultured hepatocytes by triiodothyronine. Although induction of alpha-glycerophosphate dehydrogenase did not require serum or growth hormone, the triiodothyronine effect was potentiated by insulin plus dexamethasone. This permissive effect of dexamethasone parallels its known glucocorticoid action of increasing the activity of the gluconeogenic enzyme tyrosine aminotransferase in the cultured hepatocytes. Glucagon, which also elevated tyrosine aminotransferase activity, had no effect upon the induction of alpha-glycerophosphate dehydrogenase by triiodothyronine. Since the culture medium was completely defined and triiodothyronine did not alter survival or morphology of the hepatocytes, the effects upon mitochondrial functions are direct cellular actions of the thyroid hormone.
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PMID:Effects of hormones on the maintenance and mitochondrial functions of rat hepatocytes cultured in serum-free medium. 635 97

The concentration of thyroid hormones and insulin in the serum that of glucagon in the plasma and glucose in the blood was determined at 3-hour intervals, in the course of one day, at different times of the year, in adult male rats (Wistar strain) of a conventional breed kept under standard conditions with a 12:12 h light:dark regimen. The lowest thyroid hormone and glucagon concentrations and the highest insulin and blood glucose levels were found in the winter. In various seasons, circadian oscillations of the thyroid hormones culminated in the dark part of the day and that of glucagon in the light part, with the exception of the autumn. Circadian oscillation of insulin levels culminated at different times of day during the year. The pronounced changes found in the examined hormones in the laboratory rat at various times of the year are evidently the outcome of adaptation to changes in external environmental conditions during phylogenesis. In the polarity of changes in these indicators between the winter and the summer or the spring, the laboratory rat bears the closest resemblance to wild mammals.
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PMID:Circadian oscillations of thyroid hormones, insulin and glucagon in the blood of laboratory rats in the course of the year. 638 36

Since no data are available concerning thyroid hormone levels in Snell dwarf mice from birth on, a cross-sectional study was performed of L-thyroxine (T4) and L-triiodothyronine (T3) levels in blood or serum as a function of age of several litters, starting at birth. In normal Snell mice T4 levels in blood and serum are changing with age. T4 increases during the first 2 weeks of age and declines thereafter, until adult levels of about 50 nmol/l are reached at 21 days of age. Serum T3 values are in the range of 2-3 nmol/l. They do not show such an age-related pattern. From birth on in each litter there was a clear separation between animals with low T4 levels in blood and the others. This separation was possible at all subsequent days until 9 days of age, when dwarfs can be recognized by eye. Above that age the low T4 values were associated with dwarfism. This suggests that dwarfs are hypothyroid already at birth. Serum T3 in dwarfs falls below the normal range only after 4 weeks of age, resulting in a lower T4/T3 ratio than normal. The half life time of exogenous T4 in serum of dwarfs is in the range of 13-18 h and not different from normal. For T3 t1/2 is 9.5-11.1 h. Dwarf mice become euthyroid by treatment with 0.1 microgram T4 per day. 1 microgram T4 was needed to reach a physiological level of T3. These data suggest that the peripheral conversion of T4 to T3 is slower in dwarfs than in normals. Treatment with hGH, prolactin, glucagon, insulin, testosterone and oestradiol had no influence on serum T4. As expected TSH was stimulatory. Similar results were obtained for serum T3, with the exception of prolactin which caused slightly increased levels of serum T3.
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PMID:Thyroxine and triiodothyronine levels in Snell mice. 640 74

A double-stranded cDNA library constructed from the total poly(A+) RNA of goose uropygial gland was screened for recombinants containing sequences complementary to malic enzyme mRNA. Replicate arrays of 1400 colonies were hybridized independently with 32P-labeled cDNAs copied from two populations of hepatic RNA derived from tissues which differed by about 35-fold with respect to the relative synthesis of malic enzyme. Forty-eight of the colonies which gave differential signals were further screened by hybrid-selected translation. DNA from one of these contained an insert of 970 base pairs and selected an mRNA which directed the synthesis of malic enzyme in a cell-free system. The malic enzyme sequences were subcloned into the single-stranded bacteriophage M13mp8. The subclones were used to prepare 32P-labeled single-stranded hybridization probe. Northern analysis indicated that malic enzyme mRNA from both goose and chicken is about 2100 bases in length. Hepatic malic enzyme mRNA concentration is stimulated 30- to 50-fold or more when neonatal chicks or goslings, respectively, are fed for 24 h. When added to chick embryo hepatocytes in culture, triiodothyronine stimulated malic enzyme mRNA accumulation by more than 100-fold. Glucagon inhibited the thyroid hormone-stimulated accumulation of malic enzyme mRNA by 99%. In all instances, malic enzyme mRNA concentration was closely correlated with the relative rate of malic enzyme synthesis. These results suggest that nutritional and hormonal regulation of malic enzyme synthesis occurs at the pretranslational level.
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PMID:Molecular cloning of cDNA sequences for avian malic enzyme. Nutritional and hormonal regulation of malic enzyme mRNA levels in avian liver cells in vivo and in culture. 668 83

Recent studies have shown that the addition of increasing concentrations of glucose to the medium of primary adult rat hepatocyte cultures results in the progressive induction of malic enzyme. We have undertaken experiments to determine (1) whether metabolism of glucose was an essential prerequisite for such induction, and (2) whether a specific glycolytic intermediate could be shown to constitute the proximate carbohydrate signal triggering such induction. In line with these objectives we investigated the ability of various sugars and glycolytic metabolites to induce malic enzyme in this system and assessed the influence of insulin, glucagon, and thyroid hormone (triiodothyronine, T3) on this process. Our results show that only those sugars capable of entering the cell and being metabolized induce malic enzyme (glucose, fructose, and galactose). The nonmetabolizable sugars 3-O-methylglucose and 2-deoxyglucose are ineffective. Incubation with 20 mmol/L lactate, pyruvate, dihydroxyacetone, or glycerol resulted in malic enzyme induction, whereas incubation with acetate, citrate, and alpha-ketoisocaproate was without effect. The induction by all sugars and metabolites required presence of insulin. As previously reported for glucose, addition of T3, under all metabolic conditions, resulted in a constant 3.6-fold increase in the rate of malic enzyme induction and further supports the proposal T3 acts to multiply the effect of a common carbohydrate-generated signal. Glucagon administration led to a dose-dependent inhibition of the carbohydrate effect with a half-maximal effect and maximal effect at 2 and 100 nmol/L, respectively. None of the glycolytic metabolites tested could reverse the glucagon inhibition completely.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of malic enzyme formation in hepatocyte culture by metabolites: evidence favoring a nonglycolytic metabolite as the proximate induction signal. 672 53

Perifusion of rat thyroid fragments was performed to study short-term effects of TSH, theophylline and glucagon on thyroid hormone secretion. This technique proved to be relatively convenient and sensitive, and gave reproducible results for at least 3 h, permitting precise kinetic studies of response to hormonal and pharmacological agents without any interference. There was a significant (P less than 0.001) linear correlation between the log TSH concentrations over the range 20-150 mu./ml and thyroid response. A second stimulation, using the same concentration of TSH, did not differ from the first stimulation if they were separated by an active 'washing' period of only 15 min. Theophylline also had a stimulating effect and like TSH induced an early release of the hormone fraction with a peak between 2 and 4 min, but it did not potentiate the TSH effect. Perifusion of rat thyroid fragments was found to be a useful tool for analysing dynamic effects of various substances. These effects were significant for periods of time as short as 20 min. Each thyroid preparation could be used a second time for another pharmacological or hormonal test. Our preliminary results also suggested that there was a direct glucagon effect on thyroid hormone secretion with a dose-response correlation.
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PMID:Use of the perifusion technique on rat thyroid fragments in the study of thyroid hormone secretion: short-term effects of thyrotrophin, theophylline and glucagon. 673 52

Primary cultured adult rat hepatocytes were used to study regulation of thyroid hormone deiodination. Control studies showed that these cells survived for at leas 4 d, during which time they actively deiodinated both the phenolic (5'-) and non-phenolic (5-) rings of L-thyroxine (T4),3,5,3'-triiodo-L-thyronine, and 3,3',5'-triiodothyronine. Increasing the substate concentration caused a decrease in fractional iodide release and a corresponding increase in conjugation with sulfate and glucuronide. Propylthiouracil strongly inhibited the 5'-deiodinase activity and caused only a slight decrease in 5-deiodinase activity. Thus, these monolayer-cultured cells preserved many of the properties of normal hepatocytes. Incubation with combinations of insulin, glucagon, and/or glucose for 5 h showed that insulin stimulated T4 5'-deiodination, whereas glucagon inhibited the insulin stimulation but had no effect in the absence of insulin. Glucose had no effect and did not alter the effect of the hormones. The insulin-enhanced deiodination increased between 1 and 5 h, which suggests that the previous inability to demonstrate an insulin effect was due to the short survival of the in vitro liver systems used in those studies. The present data suggest that the inhibition of T4 5'-deiodination observed during fasting, and its restoration by refeeding, may be related to the effects of feeding on insulin and glucagon release rather than on glucose per se.
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PMID:Thyroid hormone metabolism in primary cultured rat hepatocytes. Effects of glucose, glucagon, and insulin. 702 91

The role of glucocorticosteroid and thyroid hormone and of glucagon and insulin in the pre- and postnatal developmental formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase, glucose-6-phosphatase, hexokinase and glucokinase activities in rat liver was investigated. Glucocorticosteroids and a low insulin/glucagon ratio always stimulate formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase and glucose-6-phosphatase, while glucocorticosteroids and a high insulin/glucagon ratio stimulate formation of glucokinase. Thyroid hormone stimulates the formation of carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase only before birth, whereas it stimulates the formation of glutamate dehydrogenase and glucose-6-phosphatase both before and after birth. Ornithine transcarbamoylase activity is depressed after thyroid-hormone treatment before and after birth. DNA content is always decreased by glucocorticosteroids and increased by thyroid hormone. The effect of these hormones on hexokinase is complex, probably due to different responses of the constitutive isozymes. With the exception of the effects of thyroid hormone on carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase before birth, which may be indirect, the responses of enzyme activities and DNA content to treatment with glucocorticosteroid hormones, glucagon, insulin and thyroid hormone are qualitatively the same in fetuses, neonates, sucklings, weanlings and adults. Thus, the developmental profiles of the enzyme clusters reflect the changing levels of the relevant hormones. The enzymes that are stimulated by glucocorticosteroids and the insulin/glucagon ratio show increases in enzyme activity perinatally and around weaning, and relatively low activities in between, while those enzymes that are additionally stimulated by thyroid hormone differ in exhibiting relatively high activities between birth and weaning.
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PMID:Multihormonal control of enzyme clusters in rat liver ontogenesis. II. Role of glucocorticosteroid and thyroid hormone and of glucagon and insulin. 702 60

An elevated plasma glucagon concentration and reduced T3 production from T4 have both been observed in several clinical disorders, including hepatic cirrhosis, uremia, diabetes mellitus, and starvation. The question of whether glucagon has a direct effect on T3 production was studied in normal rats infused iv with [125I]T4 of [125I]T3 and 3 micrograms T4/day, using implanted minipumps. The blood [125I]T4 and [125I]T3 levels maintained a plateau between the fifth and ninth days of infusion. Each animal also received a second minipump, implanted ip, that infused either a diluant solution or 30 micrograms glucagon/100 g BW . day. After 7 days of continuous infusion, the glucagon-treated animals showed a 20% increase in plasma glucose and a 4-fold increase in plasma glucagon from baseline. However, the levels of insulin, T4, and T3 remained unchanged. The MCRs and the disposal rates of T4 and T3, calculated by the constant infusion method, showed T4 and T3 MCRs to be 0.99 +/- 0.18 and 11.25 +/- 2.52 ml/h . 100 g, respectively, and T4 and T3 disposal rates to be 68 +/- 10 and 9 +/- 2 ng/h . 100 g; there was no difference between the control animals and the glucagon-infused animals. T3 production was also determined in vitro from T4 added to a liver homogenate. Compared to control animals, the liver homogenate prepared from glucagon-infused animals showed a modestly higher T3 production rate throughout the 60-min incubation period (P = 0.025--0.05). However, the concentration of nonprotein-bound sulfhydryls was similar in the liver, kidney, brain, muscle, and heart of the two animal groups. In conclusion, glucagon does not have an important regulating role on the peripheral metabolism of thyroid hormone and T3 production in rats.
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PMID:Comparison of peripheral thyroid hormone metabolism in normal rats and in rats receiving prolonged glucagon infusion. 704 21

Synthesis of rat liver histidase is under multihormonal control; estrogen, glucocorticoid, and glucagon, via cAMP, induce this enzyme. By means of in vivo [3H]leucine incorporation into immunoprecipitated histidase, relative to that incorporated into total soluble protein, we have now demonstrated that de novo hepatic histidase synthesis, as well as catalytic activity, is selectively increased following hypophysectomy. Treatment of hypophysectomized rats with physiological levels of triiodothyronine (T3) diminished histidase synthetic rates and catalytic activities to normal levels, despite concomitant elevation in total soluble protein synthesis. Thyrotoxic doses of T3 further reduced histidase synthesis to barely measurable rates. Since thyroid hormone is under pituitary regulation, this hormone may be primary in the hypophyseal suppression of histidase. Estrogen does not induce hepatic histidase in the hypophysectomized rat. However, administration of the histidase suppressor, T3, or prolactin, which in itself has no effect on this enzyme, was ineffective in reinstating estrogen inducibility of histidase in the hypophysectomized animal. Thus, some as yet unknown hypophyseal agent is required for estrogenic inducibility of this liver enzyme.
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PMID:Effects of hypophysectomy and triiodothyronine on de novo biosynthesis, catalytic activity, and estrogen induction of rat liver histidase. 739 Oct 78


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