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 biological activity of parathyroid hormone (PTH) has been investigated by measuring intracellular accumulation of cyclic AMP (cAMP) in human kidney cortical cultures. Enzyme dispersed cortical cells from non-invaded kidney poles of patients undergoing nephrectomy for cancer were used after 5 days of primary culture. Bovine PTH (1-84) produced a significant increase of cAMP accumulation in cultured cells at a dose (53.7 ng/ml) 10-fold lower than that found for the minimal stimulatory effect when using preparations of human purified plasma membranes. The action of bovine PTH (1-84) was very rapid, a response was detected after 5 min and a ceiling effect after 30 min. Cortical cells showed a slightly lower sensitivity to synthetic bovine PTH (1-34) (half maximal increase dose: 0.66 microgram/ml), compared to bovine PTH (1-84) (half maximal increase dose: 0.32 microgram/ml), but revealed a higher sensitivity to human PTH purified from the medium of parathyroid cell cultures (half maximal increase dose: 11.2 ng/ml). Arginine-vasopressin (AVP) also increased the cAMP accumulation of kidney cortical cultured cells, with a potency and efficacy lower than that of human 'culture' PTH, while in kidney medullary cells in primary culture AVP exerted a strong response and the effect of PTH was poor or absent. Calcitonin and glucagon were weak stimulators of kidney cortical cell cAMP accumulation.
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PMID:Parathyroid hormone bioassay using human kidney cortical cells in primary culture. 628 83

We examined the relationship between PTH binding and stimulation of cAMP formation in a cell line derived from opossum kidney (OK). In the presence of isobutylmethylxanthine (1 mM) bovine PTH(1-34) [bPTH(1-34)] (244 nM) stimulated cAMP accumulation in confluent cultures up to 40-fold over basal; this response to PTH was stable for 35 passages. The concentration of bPTH(1-34) required to raise cell cAMP levels half-maximally was 5-12 nM. Binding of [125I]bPTH(1-34) to OK cells was saturable; Scatchard analysis of competitive binding data yielded a dissociation constant (KD) = 6 +/- 2 nM, with 1.0 pmol binding sites/mg cell protein. Under steady state binding conditions 89% of labeled PTH remained precipitable by 10% trichloroacetic acid, suggesting minimal metabolism of the hormone. The PTH antagonist (8Nle, 18Nle, 34Tyr)bPTH(3-34)amide competed for [125I]bPTH(1-34) binding sites and inhibited the action of bPTH(1-34) to raise cAMP levels. The intact PTH molecule, bPTH(1-84), and the weak agonist hPTH(1-34) synthesized by Brewer were both less potent than bPTH(1-34) (6 times and 30 times, respectively) with regard to binding and cAMP production. Calcitonin and arginine vasopressin did not bind to PTH receptors but raised cAMP levels in OK cell cultures 3- and 10-fold, respectively; neither glucagon nor ACTH(1-24) influenced PTH binding of cAMP in OK cells. Varying the extracellular calcium concentration in the medium bathing cells did not influence basal or PTH-stimulated cAMP generation. These data suggest that PTH receptors in OK cells are of high affinity, are selective for PTH, and are coupled to adenylate cyclase. This established epithelial cell line provides a model in which to study the mechanism of action of PTH in the kidney.
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PMID:Parathyroid hormone receptors coupled to cyclic adenosine monophosphate formation in an established renal cell line. 632 Nov 47

Glucagon, porcine calcitonin, and mithramycin were given to patients with Paget's disease of bone. There was rapid complete relief of bone pain accompanied by biochemical improvement or normalization in all cases. Calcitonin and glucagon appear to have additive properties in Paget's disease and the use of the 3 drugs in combination may reduce the incidence of side effects and the development of "drug resistance". The cost of treatment might also be reduced if periodic treatment as demonstrated in Case 1 is used.
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PMID:Control of osteitis deformans using glucagon, calcitonin, and mithramycin. 645 56

The effects of salmon calcitonin on the renal concentrating mechanism were investigated in homozygous DI Brattleboro rats. The levels of peptide hormones believed to produce the same physiological responses as antidiuretic hormone on the thick ascending limb (glucagon, parathyroid hormone, and calcitonin) and the cortical collecting ducts (calcitonin) were reduced by acute thyroparathyroidectomy and somatostatin administration. In these hormone-deprived animals, the corticomedullary concentration gradient was almost abolished; the (F/P)osmol at the tip of the juxtamedullary nephrons was 1.19 +/- 0.05. Calcitonin administration restored the gradient [(F/P)osmol = 1.85 +/- 0.14] and simultaneously absolute and fractional water excretion fell significantly despite the concomitant rise in the glomerular filtration rate. It is concluded that 1) in the hormone-deprived animal, calcitonin administration consistently enhances the corticomedullary concentration gradient, and 2) the effects of hormone deprivation and calcitonin administration on the urinary concentrating mechanism are compatible with direct stimulation by calcitonin of electrolyte reabsorption along the thick ascending limb and/or of the water permeability of the cortical collecting ducts.
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PMID:Effects of calcitonin on the renal concentrating mechanism. 662 11

The effects of Ca2+ and calcitonin infusions on circulating glucagon, glucose, C-peptide, Ca2+, and calcitonin were investigated in hyper-glucagonaemic insulin-dependent diabetics. In 14 insulin-deprived diabetics and 12 healthy volunteers 2h infusions of saline (0.154 mol/1), Ca2+ (0.375 mmol/kg body weight), and calcitonin (4.5 IU/kg body weight) were performed. There were no significant changes during saline infusion. In the diabetics, Ca2+ infusions induced a rise of plasma Ca2+ up to 3.2 +/- 0.1 mmol/1 and a fall of circulating glucagon (-26.4 +/- 5.7%; p less than 0.001) and glucose (-23.3 +/- 3.6%; p less than 0.05). Plasma calcitonin rose to twice basal values (p less than 0.025). During calcitonin infusions plasma Ca2+ decreased slightly to 2.1 +/- 0.2 mmol/1; a fall was found in both glucose (-24.4 +/- 4.0%; p less than 0.05) and circulating glucagon (-22.5 +/- 4.3%; p less than 0.001). Two groups of 6 healthy volunteers were subjected to saline and Ca2+, or to Ca2+ and calcitonin infusions. Both Ca2+ and calcitonin infusions induced a fall of serum insulin (-30.1 +/- 6.6%; p less than 0.05). Calcitonin depressed circulating glucagon by -18.6 +/- 4.4% (p less than 0.025), whereas during Ca2+ infusions glucagon decreased only by -6.5 +/- 1.9% (p greater than 0.1). We conclude from our results that an increase of circulating calcitonin induced by Ca2+ infusions or by exogenous calcitonin administration appears to depress elevated circulating glucagon and glucose in insulin-dependent diabetics.
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PMID:Effects of calcium and calcitonin on circulating levels of glucagon and glucose in diabetes mellitus. 702 28

The present study was aimed at investigating the effect of calcitonin on plasma glucose, C-peptide, glucagon and growth hormone (GH) responses to arginine in insulin-dependent diabetic subjects. For this purpose, 6 insulin-requiring diabetics were submitted to an arginine tolerance test twice, in basal conditions and during the simultaneous infusion of salmon calcitonin (100 MRC) plus arginine in random order. Calcitonin caused a clear inhibition of the plasma glucose rise triggered by the amino acid, without significant modifications of the plasma C-peptide and glucagon responses. A significant rebound of plasma glucose was seen after calcitonin was stopped. Plasma GH rise following arginine administration was significantly inhibited by calcitonin. These findings suggest some positive interferences of calcitonin with the arginine-induced plasma glucose increase in insulin-dependent diabetes.
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PMID:Effect of Calcitonin on plasma glucose, C-peptide, glucagon and growth hormone responses to arginine in insulin-dependent diabetic subjects. 702 89

Neurotensin (NT), peptide YY (PYY), and several peptides derived from proglucagon are promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal, thus suggesting that release of these peptides is partly under neural and/or hormonal control. Our previous studies conducted with a model of isolated vascularly perfused rat colon showed that colonic L cells are highly responsive to several transmitters of the gut and to the hormonal peptide GIP. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may also modulate the secretory activity of the ileal L cells, various intestinal regulatory peptides and neurotransmitters were administered intraarterially for 30 min in the isolated vascularly perfused rat ileum preparation. The secretory activity of the ileal N cells was comparatively assessed. The release of NT, PYY, and glucagon-like peptide-1 (GLP-1) in the portal effluent was measured with specific RIAs. The muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M provoked a biphasic release of PYY, GLP-1, and NT, consisting of an early peak followed by a sustained response. Similarly, bombesin (10(-7) M) induced a marked biphasic release of PYY and GLP-1. In contrast, the NT response was essentially monophasic, characterized by an early peak secretion. Tetrodotoxin did not modify the bombesin-induced release of PYY, GLP-1, and NT. The beta-adrenergic agonist isoproterenol at a concentration of 10(-6) M induced a transient rise in portal PYY and GLP-1 concentrations, whereas the effect on NT release was clearly biphasic. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise in PYY, GLP-1, and NT immunoreactivities in the portal effluent (peaks at 600%, 500%, and 550% of the basal values, respectively, 4 mi n after the start of infusion). Intraarterial infusion of GIP over the concentration range (0.5-3 nM) evoked a significant increase in portal concentration of the three peptides only at the threshold concentration of 3 nM. Secretin (50 pM) or cholecystokinin (50 pM) did not affect the release of ileal hormones. In conclusion, ileal L and N cells respond to a variety of transmitters of the gut. The pattern of peptide release depends on the cell type studied. The two cosynthesized peptides, PYY and GLP-1, appear to be cosecreted in the conditions of the present study.
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PMID:Regulation of glucagon-like peptide-1-(7-36) amide, peptide YY, and neurotensin secretion by neurotransmitters and gut hormones in the isolated vascularly perfused rat ileum. 758 57

Glucagon-like peptide-1 (GLP-1) is promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may be involved in the early phase of meal-induced GLP-1 secretion, various intestinal regulatory peptides and neurotransmitters of the gut were administered intraarterially in the isolated vascularly perfused rat colon preparation. The release of GLP-1 in the portal effluent was measured by a specific RIA. Intraarterial infusion of glucose-dependent insulinotropic peptide (GIP) over the concentration range 0.25-1 nM evoked a dose-dependent release of GLP-1, with a maximal response of 350% of the basal value. Tetrodotoxin did not modify the GIP-induced release of GLP-1. Secretin or cholecystokinin did not stimulate the secretion of GLP-1. Bombesin (10(-9)-10(-7) M) provoked a dose-dependent release of GLP-1, consisting of an early peak, followed by a sustained response. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise of GLP-1 immunoreactivity in the portal effluent (peak at 800% of the basal value 10 min after the start of infusion). Similarly, the beta-adrenergic agonist isoproterenol at concentrations of 10(-7) and 10(-6) M provoked a pronounced release of GLP-1 (peak at 500% of the basal value with 10(-6) M isoproterenol). Finally, the muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M evoked a gradual increase in GLP-1 immunoreactivity, which reached a maximal value (900% over basal) at the end of the 30-min infusion period. The lowest concentration of bethanechol used in the present study (10(-5) M) did not increase portal GLP-1 immunoreactivity over the basal value. Tetrodotoxin did not modify the bethanechol-, isoproterenol-, calcitonin gene-related peptide-, or bombesin-induced GLP-1 release. In conclusion, the present study conducted with the isolated vascularly perfused rat colon shows that there are interactions between the two most potent incretins, GIP and GLP-1, probably through an enteroendocrine pathway. Additionally, several transmitters of the gut are potent stimulants of GLP-1 release and, therefore, represent potential tools in the treatment of the noninsulin-dependent diabetes mellitus.
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PMID:Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. 798 23

We studied the hormonal secretion of a human mixed follicular and medullary carcinoma. Thyroglobulin (Tg) secretion, especially by large cells and sometimes by small ones, was visualized with immunoenzymatic staining. Calcitonin (CT) was produced by small spindle-shaped cells. Moreover, immunofluorescence double staining performed on the resected thyroid tissue showed the secretion of both Tg and CT in a small number of cells. The cells lost their hormonal secretion after 2 months of culture. Hormonal secretion was modulated by different additives in the medium. Tg secretion was induced when TSH was added to the culture medium; the maximal effect was produced with the addition of 1 mU TSH/ml and 1 microM cortisol, which potentiated the effect of TSH on Tg production. A durable Tg secretion was obtained by embedding the cells in Engelbretch-Hohn-Swarn (EHS) tumour matrix. The CT production was reinduced by the addition of 4 mM Ca2+, 1 microM glucagon and 1 microM cortisol to the culture medium. These findings show that different cells are found in a mixed follicular and medullary carcinoma, some of which can secrete both CT and Tg. They can remain differentiated for a long period after being embedded in EHS tumour matrix with Ca2+ and hormonal components.
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PMID:Hormonal study of a human mixed follicular and medullary thyroid carcinoma. 824 Jun 72

Calcitonin gene-related peptide (CGRP) shares about 46% and 20% amino acid sequence homology with islet amyloid polypeptide (IAPP) and salmon calcitonin (sCT). We investigated whether these related peptides could cross-react with the specific binding of 125I-[His]hCGRP I to the CGRP receptor in hamster insulinoma cell membranes. A rapid dissociation of membrane bound 125I-[His]hCGRP I could be induced in the presence of 1 microM chicken CGRP (cCGRP). The specific 125I-[His]hCGRP I binding was inhibited by the related peptides and their half-maximal inhibitory concentrations (IC50) were: cCGRP (0.1 nM), rat CGRP I and human CGRP I and II (1.0-2.0 nM), fragment of hCGRP I (8-37) (150 nM), human IAPP (440 nM). The non-amidated form of hIAPP; human diabetes-associated peptide (hDAP) did not inhibit the binding of 125I-[His]hCGRP I and sCT was only effective at a high concentration (1 microM). Binding of 125I-[His]hCGRP I was dose dependently inhibited by guanosine-5'-O-(3-thiotriphosphate) or (GTP gamma S) and a 70% reduction of binding was obtained with 0.1 mM GTP gamma S. The IC50 value of cCGRP (0.1 nM) was increased 100-fold in the presence of 0.1 mM GTP gamma S. Human CGRP I and cCGRP at 2.5 microM did not stimulate the activity of hamster insulinoma cell membranes adenylate cyclase, while glucagon (1 microM) induced a 2-fold increase. Thus, specific CGRP receptors present in hamster beta cells are associated with G protein (s) and IAPP can interact with these receptors. These results and the observation that cCGRP and hCGRP I did not influence adenylate cyclase activity provide further evidence for CGRP receptor subtypes.
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PMID:Characterization of specific calcitonin gene-related peptide receptors present in hamster pancreatic beta cells. 830 33


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