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)

Thyroid hormone regulates the expression of ventricular myosin isoenzymes by causing an accumulation of alpha-myosin heavy chain (MHC) mRNA and inhibiting expression of beta-MHC mRNA. However, the mechanism of thyroid hormone action has been difficult to examine in vivo because of its diverse actions. Accordingly, hormonal control of expression of six MHC isoform mRNAs and cardiac and skeletal alpha-actin mRNAs was studied in primary cultures of fetal rat heart myocytes grown in defined medium. The results indicate that in the absence of thyroid hormone, cultured heart cells express predominantly beta-MHC and cardiac alpha-actin mRNAs. Addition of 3,5,3'-triiodo-L-thyronine (T3) caused a rapid induction of alpha-MHC mRNA and decreased beta-MHC mRNA levels without affecting the skeletal muscle MHC mRNAs. There was an almost parallel change in the myosin isoenzymes. Cardiac alpha-actin mRNA levels were transiently increased by T3 treatment, but skeletal alpha-actin was unaffected. Elimination of insulin and epithelial growth factor from the medium did not alter the effects of T3 on cardiac MHC mRNA expression. Addition of various adrenergic agents to the medium had no appreciable effect on cardiac MHC mRNA expression despite the presence of functionally coupled alpha- and beta-adrenergic receptors. Addition of steroid hormones, muscarinic agents, and glucagon to the medium also had no effect. Thus, under defined conditions, T3 is able to regulate MHC gene expression at a pretranslational level without the need for other exogenous factors.
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PMID:Hormonal regulation of myosin heavy chain and alpha-actin gene expression in cultured fetal rat heart myocytes. 288 58

Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects.
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PMID:Clinical evaluation of SMS 201-995. Long-term treatment in gut neuroendocrine tumours, efficacy of oral administration, and possible use in non-tumoural inappropriate TSH hypersecretion. 289 35

In order to investigate effects of thyroid hormone on ketone bodies metabolism, fasting levels of serum ketone bodies, serum free fatty acids (FFA), serum insulin (IRI), plasma glucagon (IRG) and plasma glucose were examined in 29 untreated patients with hyperthyroidism and 20 healthy subjects. In 21 patients the levels of serum ketone bodies were re-examined when euthyroidism was achieved after treatment. In all of healthy subjects and 17 patients changes in the levels of serum ketone bodies after oral glucose load were examined. The results were as follows: 1). Fasting levels of serum FFA and total ketone bodies (TK), acetoacetate (AcAc), 3-hydroxy-beta-butylate (3OHBA), ratio of 3OHBA to AcAc in the patients were significantly higher than those in healthy subjects. The levels of IRI, IRG or ratio of IRG to IRI in the patients were not different from those in healthy subjects. In the patients, the fasting level of TK was significantly correlated with the level of FFA. 2). After oral glucose load the levels of TK and FFA in the patients decreased gradually. 3). The fasting levels of TK and FFA in the patients decreased when euthyroidism was achieved after treatment. It was suggested that the fasting levels of serum ketone bodies in patients with hyperthyroidism elevated probably due to activated lipolysis.
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PMID:[Studies on serum ketone bodies in patients with hyperthyroidism]. 306 96

Injections of 10 micrograms/kg thyrotropin-releasing hormone (TRH) 150 microliter intracisternally (i.c.) in conscious rabbits evoked behavioral excitation and compulsive scratching, tachypnoea, an increase of heart rate and blood pressure, oxygen consumption and hyperthermia. TRH i.c. significantly increased free thyroid hormone and calcitonin secretion during depressed thyrotropin (TSH) secretion. The rise of calcitonin correlated with a fall of serum calcium. The ergotropic function of TRH i.c. was further demonstrated by rapid increases of glucagon, serum glucose, free fatty acid and free glycerol, with a delayed rise of insulin depending on glucose levels. The increases of free thyroid hormones, calcitonin, cortisol and lipolysis following TRH i.c. were augmented after spinal transection, while glucagon secretion increased at a slower rate, however, not accompanied by rises of glucose and insulin. Behavioral excitation and lipolysis were augmented by TRH i.c. after total thyroidal denervation, which completely prevented the rise in thyroid hormone and calcitonin secretion, although the thyroid follicles and C cells responded properly to TSH. Section of all thyroidal nerves except the recurrent laryngeal nerve reduced mainly calcitonin secretion following TRH i.c., while the behavioral, autonomic and other endocrine responses were augmented. Additional abdominal vagotomy in these rabbits diminished glucagon secretion by about 50% without significantly changing the other effector responses. Taking 125I-labelled TRH concentration in the cerebrospinal fluid at the site of i.c. injection as 100%, then 58% of TRH penetrated into outer parts of the dorsal and ventral medulla oblongata and pons, and 8% into the neuropil of the aqueductal region. Radioactivity in other brain areas including the hypothalamus was below 1%, while the hypophysis was practically devoid of radiolabelled TRH. It is suggested that the observed behavioral, autonomic and endocrine activity pattern elicited by injection of TRH into the cisterna magna was caused by excitation of neurons confined to that compartment and was mediated by pathways of the reticular formation of the lower brainstem, with the concept that TRH-containing neurons are intrinsic excitatory constituents of the 'activating reticular system'.
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PMID:Selective autonomic nervous control of thyroid hormone and calcitonin secretion during metabolic and cardiorespiratory activation by intracisternal thyrotropin-releasing hormone (TRH). 314 96

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum Triiodothyronine (T3) and a rise in reverse T3 (rT3) in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is suppressed by exogenous administration of L-thyroxine (L-T4) in appropriate dosage, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in euthyroid healthy subjects after administration of L-T4 for 12 weeks. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4 and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.01) and a marked rise in rT3 (P less than 0.01) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Therefore, this study demonstrates that changes in serum T3 and rT3 caused by hyperglucagonemia may be secondary to altered thyroid hormone metabolism in peripheral tissues and not due to altered release by the thyroid gland, since the release of thyroid hormones is suppressed by exogenous L-T4 administration.
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PMID:Decline of T3 and elevation in reverse T3 induced by hyperglucagonemia: changes in thyroid hormone metabolism, not altered release of thyroid hormones. 318 70

The responses of plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading (0.1 g/kg) were observed in 9 control subjects and 7 hyperthyroid patients, before and after restoration of thyroid function to normal. Despite the persistence of impaired glucose response to alanine, the blunted IRI and IRG responses in the hyperthyroid state were improved with a significant reduction in fasting IRI and IRG after treatment. Markedly increased FFA following alanine loading in hyperthyroid patients was reduced after treatment, but the FFA concentration remained greater than in the control subjects. We tentatively conclude that the impaired alpha and beta-cell responses to alanine were temporarily induced by the direct and/or indirect effects of thyroid hormone excess.
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PMID:Changes in plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading in hyperthyroid patients. 333 25

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum T3 and a rise in reverse T3 in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is inhibited in primary hypothyroidism and is almost totally suppressed following L-thyroxine replacement therapy, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in subjects with primary hypothyroidism who were rendered euthyroid by appropriate L-thyroxine replacement therapy for several years. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4, and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.05) and a marked rise in rT3 (P less than 0.05) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Since, the release of thyroid hormones is suppressed by exogenous LT4 administration in these subjects; we conclude that changes in serum T3 and rT3 observed following glucagon administration reflect altered thyroid hormone metabolism in peripheral tissues and not altered release by the thyroid gland.
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PMID:Lowering of T3 and rise in reverse T3 induced by hyperglucagonemia: altered thyroid hormone metabolism, not altered release of thyroid hormones. 342 67

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murine species that, due to their altricial (rat) and precocial (spiny mouse) modes of development, differ in the developmental timing of birth. A comparison between the developmental profiles of plasma glucagon, insulin, thyroxine, triiodothyronine, and glucocorticosteroid hormone was carried out to elucidate the question to what extent these hormonal profiles were related to the timing of birth. Although corticosterone is the major circulating glucocorticosteroid in rat, only cortisol was found in the spiny mouse. The onset of increases in glucocorticosteroid and thyroid hormone levels occurred at the same developmental time points in both species. A neonatal increase in triiodothyronine levels was observed in the spiny mouse only. In both species the immediate perinatal period was characterized by decreases in the ratio of insulin and glucagon levels and the level of glucocorticosteroids. The observed developmental patterns of hormonal levels were found to be consistent with the observed developmental pattern of enzymic maturation in the respiratory and gastrointestinal tract, which play a critical role in the adaptation to the extrauterine environment.
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PMID:Hormones in perinatal rat and spiny mouse: relation to altricial and precocial timing of birth. 352 60

The activity of hepatic fatty acid synthase (EC 2.3.1.85) correlates positively with the rate of synthesis of long-chain fatty acids. Thus, in a starved chick, both the rate of fatty acid synthesis and the activity of fatty acid synthase are low. Feeding stimulates both processes. The increase in fatty acid synthase activity caused by feeding is due to an increase in the concentration of enzyme protein, which in turn is caused by an increase in the rate of synthesis of the enzyme. Using fatty acid synthase cDNA clones isolated in our laboratory, we showed that feeding causes a rapid increase in the level of fatty acid synthase mRNA. Increased transcription of the fatty acid synthase gene precedes the increase in fatty acid synthase mRNA level caused by feeding, which indicates regulation at the level of transcription. The feeding-induced stimulation of fatty acid synthase can be mimicked in culture by incubating chick embryo hepatocytes with insulin and thyroid hormone. Glucagon inhibits the increase caused by insulin and thyroid hormone. Enzyme synthesis is the regulated step. In hepatocytes in culture, thyroid hormone stimulates and glucagon inhibits the accumulation of fatty acid synthase mRNA. Insulin has only a small stimulatory effect on mRNA level despite a large stimulation of the synthesis of fatty acid synthase. Thus, thyroid hormone and glucagon regulate enzyme level at a pretranslational step, whereas insulin regulates the translation of fatty acid synthase mRNA. We conclude that complex hormonal regulation of the production and translation of fatty acid synthase mRNA underlies the dietary regulation of enzyme synthesis observed in intact animals. Future work will involve isolation of cloned genomic DNA for the fatty acid synthase gene and identification of nucleotide sequences involved in the regulation of this gene.
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PMID:Regulation of the gene for fatty acid synthase. 352 33

A non-neoplastic syndrome of inappropriate secretion of TSH (ITSHS) was diagnosed in a hemithyroidectomized and clinically euthyroid 44-yr-old man, who also exhibited limping (Perthes' disease), genu valgum, pes supinatus and lateral nystagmus. Computed tomography demonstrated an enlarged sella turcica due to empty sella. Baseline serum T3, T4, free T3, free T4 and TSH fluctuated between 179 and 274 ng/dl, 6.0 and 13.2 micrograms/dl, 4.2 and 6.0 pg/ml, 7.6 and 15.3 pg/ml, and 4.3 and 33.0 microU/ml, respectively. Serum alpha-TSH subunit was repeatedly normal (0.36-0.69 ng/ml) over the follow-up period (greater than 3 yr). No changes in serum liver enzymes and lipids were observed after thyroid hormone administration, whereas red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) and urinary OH-proline were slightly enhanced during 120 micrograms/day L-T3 regimen. This also resulted in an inappropriately normal glucagon-stimulated cAMP levels. Tachycardia was experienced only during L-T3 and very high L-T4 dose treatments. Therefore, the patient showed some evidence for thyroid hormone peripheral refractoriness. Patient's TSH was physiologically responsive to agents (thyrotropin releasing hormone, methimazole, the dopamine antagonists domperidone and sulpiride) known to elicit its release into circulation, while it responded paradoxically to those which normally inhibit TSH secretion. In fact, the infusion of somatostatin (320 micrograms/h) or dopamine (4 micrograms/Kg/min), and the oral administration of bromocriptine or nomifensine (two dopamine agonists) or corticosteroids (dexamethasone) provoked an unexpected elevation of both unstimulated and TRH-stimulated TSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal daily periodicity of serum thyrotropin (TSH) and evidence for defective TSH suppression in a case of non-neoplastic syndrome of inappropriate TSH secretion. 358 59


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