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)

Laboratory rodents can be induced to overeat voluntarily when exposed to a choice of highly palatable human foods so-called "cafeteria diet". The hyperphagia of these animals is associated with marked increases in energy expenditure and reduced levels of energetic efficiency. Increases in Diet-Induced-Thermogenesis (DIT) in response to overfeeding have been demonstrated in several species including man. The studies with the cafeteria-fed rats confirm the large potential for DIT in young animals. In older (26-week-old rats) a dramatic decline in the capacity for DIT is observed. Increases in energy expenditure resulting from hyperphagia appear to be mediated by the sympathetic nervous system, which causes activation of heat production in brown adipose tissue (BAT). The high thermogenic potential of BAT is due to the physiological uncoupling of oxidative phosphorylation in the inner mitochondrial membrane. This activity is enhanced by overfeeding, which causes hypertrophy. DIT and BAT are controlled by hormonal action: noradrenaline appears to be the primary activator of BAT and insulin may be required for DIT and may even activate thermogenesis. Other hormones such as glucagon, thyroid, melatonin, TSH, endorphins and sex hormones are also implicated in one way or another in the regulation of energy balance and the control of thermogenesis.
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PMID:The role of brown fat in diet-induced thermogenesis. 346 Sep 73

Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32-52 years, TSH-values 66-200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin. C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.
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PMID:Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism. 351 23

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

Euthyroid sick syndrome is characterized by low serum T3 and raised reverse T3 (rT3). Most of the states with this syndrome are also documented to manifest hyperglucagonemia. Furthermore, several recent studies have suggested that glucagon may play a role in T4 monodeiodination in some of these states such as starvation and uncontrolled diabetes mellitus. Therefore, hyperglucagonemia was induced by intravenous glucagon administration in euthyroid healthy volunteers and thyroid hormone levels were determined at frequent intervals up to six hours. Plasma glucose and insulin rose promptly on glucagon administration, thus establishing the physiologic effect of glucagon. Serum T4, free T4, T3 resin uptake, and TSH concentrations remained unaltered throughout the study period. Serum T3 declined to a significantly low level (P less than 0.05) between 60-90 minutes. Serum rT3 rose significantly (P less than 0.05) by four hours and the rise was progressive till the end of the study period. Therefore, these results suggest that hyperglucagonemia may be one of the factors responsible for lowering of T3 and a rise in rT3 in euthyroid sick syndrome.
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PMID:Glucagon administration induces lowering of serum T3 and rise in reverse T3 in euthyroid healthy subjects. 391 May 31

A possible role for adenylcyclase in insulin secretion was investigated. Isoproterenol, a predominantly beta-adrenergic agent, when mixed with an alpha-adrenergic blocking agent (phenoxybenzamine), stimulated insulin secretion from pieces of the rat's pancreas in vitro. Theophylline, caffeine, 3'5'-cyclic AMP, glucagon, adrenocorticotropin (ACTH), and thyrotropin (TSH), all of which are thought to act through the adenylcyclase systems in the liver and adipose tissue, also stimulated insulin secretion in vitro; oxytocin and vasopressin, which do not stimulate lipolysis in adipose tissue, were inactive. In all cases, stimulation of insulin secretion could not be detected when glucose was absent or present in only low concentrations (less than 100 mg/100 ml) and was maximal at high levels of glucose (300 mg/100 ml). When pancreatic tissue was obtained from normoglycemic rats and contained no detectable glycogen in the Islets, the stimulant effects of glucose and of theophylline were reduced or abolished by mannoheptulose and 2-deoxyglucose. When tissue was derived from rats infused for 8-10 hr with glucose and contained glycogen, theophylline, even in the absence of glucose, stimulated secretion and this effect was reduced by 2-deoxyglucose but not by mannoheptulose. It is suggested that the beta-cell contains an adenylcyclase system through which phosphorylase and possibly phosphofructokinase could be activated; and that insulin secretion could depend upon and be regulated by hormones and other substances which influence the rate at which glycolysis proceeds within the beta-cell.
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PMID:A possible role for the adenylcyclase system in insulin secretion. 429 54

1. The epigastric adipose tissue of rabbits has been prepared so that the effects of close arterial injections and infusions on blood flow and release of free fatty acids (FFA) can be studied. The effects of pharmacologically active agents and hormone preparations have been investigated.2. Release of FFA was stimulated by synthetic adrenocorticotrophic hormone (ACTH), alpha and beta melanophore stimulating hormone (MSH), porcine growth hormone, glucagon, thyrotropic hormone (TSH) and luteotropic hormone (LTH). Single injections of fat-mobilizing agents produce a sustained rise in the release of FFA.3. Although pitressin caused release of FFA, synthetic vasopressin and oxytocin failed to do so. The FFA releasing activity of pitressin has therefore been attributed to a contaminant.4. Catecholamines were found not to stimulate release of FFA from this fat depot, but were found to increase plasma FFA when infused intravenously.5. Injections of acetylcholine, histamine, bradykinin, 5-hydroxytryptamine, synthetic arginine vasopressin, and lysine vasopressin, oxytocin, angiotensin and FSH did not stimulate release of FFA although marked effects on blood flow were produced.6. Injections of prostaglandin E(1) gave sustained increases in blood flow, and inhibited FFA release when stimulated by growth hormone.7. The mobilization of FFA is sometimes associated with an increased rate of blood flow.
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PMID:The mobilization of free fatty acids from rabbit adipose tissue in situ. 430 78

This chapter has covered a wide range of different actions of methylxanthines. They are able to slightly reduce the tone of the lower esophageal sphincter. This is of little concern in the normal individual, but in patients with a reduced initial tone it might lead to heartburn. Coffee intake has been associated with gastritis, but the role of methylxanthines in this effect is obscure. High doses of methylxanthines are also known to be emetic. Practically every function in the intestine can be influenced by high doses of methylxanthines, but the mechanisms involved and the biological significance remain largely obscure. Although in vitro studies with high doses of methylxanthines have demonstrated effects on secretion from salivary glands and exocrine pancreas, there is little evidence that this is clinically important in man. There is also small effects on insulin, glucagon, and TSH secretion. There is a consistent effect on fatty acid mobilization from adipose tissue, which may be of importance, eg, by improving physical performance and by increasing the overall metabolic rate. There is also some evidence for long-term effects on fat depots. By contrast, the effects on carbohydrate metabolism are much less prominent and reproducible, and may to some extent be secondary to altered lipid metabolism. Despite more than a century of effort to elucidate the actions of methylxanthines in man, one of the major conclusions to be drawn is that there is a need for further studies. In view of the newer ideas about the mechanism of action of caffeine and other methylxanthines, careful studies, especially of long-term effects of methylxanthines on several aspects of gastrointestinal function, on calcium homeostasis, on body composition, and on physical performance, would be desirable.
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PMID:Gastrointestinal and metabolic effects of methylxanthines. 608 44

The widespread occurrence of opioid peptides and their receptors in brain and periphery correlates with a variety of actions elicited by opioid agonists and antagonists on hormone secretion. Opioid actions on pituitary and pancreatic peptides are summarized in Table 1. In rats opioids stimulate ACTH and corticosterone secretion while an inhibition of ACTH and cortisol levels was observed in man. In both species, naloxone, an opiate antagonist, stimulates the release of ACTH suggesting a tonic suppression by endogenous opioids. In rats, a different stimulatory pathway must be assumed through which opiates can stimulate secretion of ACTH. Both types of action are probably mediated within the hypothalamus. LH is decreased by opioid agonists in many adult species while opiate antagonists elicit stimulatory effects, both apparently by modulating LHRH release. A tonic, and in females, a cyclic opioid control appears to participate in the regulation of gonadotropin secretion. Exogenous opiates potently stimulate PRL and GH secretion in many species. Opiate antagonists did not affect PRL or GH levels indicating absence of opioid control under basal conditions, while a decrease of both hormones by antagonists was seen after stimulation in particular situations. In rats, opiate antagonists decreased basal and stress-induced secretion of PRL. Data regarding TSH are quite contradictory. Both inhibitory and stimulatory effects have been described. Oxytocin and vasopressin release were inhibited by opioids at the posterior pituitary level. There is good evidence for an opioid inhibition of suckling-induced oxytocin release. Opioids also seem to play a role in the regulation of vasopressin under some conditions of water balance. The pancreatic hormones insulin and glucagon are elevated by opioids apparently by an action at the islet cells. Somatostatin, on the contrary, was inhibited. An effect of naloxone on pancreatic hormone release was observed after meals which contain opiate active substance. Whether opioids play a physiologic role in glucose homeostasis remains to be elucidated.
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PMID:Endocrine actions of opioids. 608 80

The present study was undertaken to determine the plasma levels of somatostatin-like immunoreactivity (SLI) during constant infusion of graded concentrations of synthetic somatostatin-14 (S-14); to determine the half-life (t1/2) and metabolic clearance rate (MCR) of SLI; to correlate the plasma SLI levels with the degree of inhibition of pituitary and islet hormone secretion and to establish whether the plasma SLI levels capable of inhibiting pituitary and islet hormone secretion fall into the physiological range. Four normal subjects on separate occasions were each infused with saline or S-14 (25,50 and 75 micrograms/h) at a constant rate for 2 1/2 h. Thirty min following the infusions, TRH (200 micrograms) and arginine (0.5 g/kg) were given i.v. Blood samples were drawn every 15 min for measurement of GH, TSH, insulin, glucagon and SLI (by RIA of acid-ethanol extracted plasma) and at rapid intervals for 10 min after stopping the infusions for measurement of SLI disappearance. During S-14 infusions, plasma SLI rose rapidly, reached a plateau from 15-150 min and declined rapidly on cessation of the infusions with a mean t 1/2 of 2.72 +/- 0.45 min. Mean plateau SLI levels were: 149 +/- 3 pg/ml (25 micrograms/h), 465 +/- 35 pg/ml (50 micrograms/h), and 1244 +/- 71 pg/ml (75 micrograms/h). SLI was cleared rapidly but the MCR exhibited a dose-dependent decrease from 3225 +/- 699 ml/min for the 25 micrograms infusion to 1249 +/- 241 ml/min for the 75 micrograms/h infusion (P less than 0.05). The 25 micrograms/h infusion dose produced near-maximal suppression of GH secretion and inhibited insulin secretion but not TSH or glucagon secretion. The intermediate dose significantly inhibited GH, TSH, and insulin but not glucagon whereas the 75 micrograms/h infusion suppressed all four hormones. In six normal subjects endogenous plasma SLI rose from a basal value of 32.5 +/- 4.9 pg/ml to 75.5 +/- 9.0 pg/ml following ingestion of a mixed meal. This level was 50% of that resulting from the 25 micrograms/h infusion and which suppressed GH almost completely. We concluded that: Infused S-14 is cleared rapidly and decays with a short t 1/2; S-14 inhibits its own MCR; The somatotrophs are the most sensitive to S-14 inhibition, followed by the thyrotrophs and the B-cells (approximately equally) followed by the A-cells; Fluctuations in plasma SLI occurring physiologically may influence GH and possibly other S-14 sensitive cells by an endocrine mechanism.
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PMID:Infusion of graded concentrations of somatostatin in man: pharmacokinetics and differential inhibitory effects on pituitary and islet hormones. 614 13

Incorporation of 3H-uridine by RNA in Tetrahymena was differently influenced by insulin, glucagon, follicle-stimulating hormone (FSH), thyrotropic hormone (TSH), adrenocorticotropic hormone (ACTH) and chorion-gonadotropic hormone (PMSG). TSH caused it to increase considerably and durably after an initial depression, while glucagon caused it to rise over the control throughout. Insulin, and especially PMSG, depressed the incorporation of label considerably, the latter to 3-6% of the control value by 120 min. ACTH and FSH accounted for an initial depression of RNA synthesis which, however, returned to normal 30 min after treatment. Remarkably, while the chemically similar hormones acted differently, insulin and glucagon showed the same trend of positive and negative influence, respectively.
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PMID:Effect of polypeptide hormones (insulin, thyrotropin, gonadotropin, adrenocorticotropin) on RNA synthesis in Tetrahymena, as assessed from incorporation of 3H-uridine. 618 2


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