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 synthetic 1-34 fragment of human parathyroid hormone (1-34hPTH) stimulated glucose production in isolated rat hepatocytes. The effect of 1-34hPTH was dose-dependent and 10(10) M-1-34 hPTH elicited the maximum glucose output, which was approx. 80% of that by glucagon. Although 1-34hPTH induced a small increase in cyclic AMP production at concentrations higher than 10(-9) M, 10(-10) M-1-34hPTH induced the maximum glucose output without significant elevation of cyclic AMP. This is in contrast to the action of forskolin, which increased glucose output to the same extent as 10(-10) M-1-34hPTH by causing a 2-fold elevation of cyclic AMP. In addition to increasing cyclic AMP, 1-34hPTH caused an increase in cytoplasmic free calcium concentration ([Ca2+]c). When the effect of 1-34hPTH on [Ca2+]c was studied in aequorin-loaded cells, low concentrations of 1-34hPTH increased [Ca2+]c: the 1-34hPTH effect on [Ca2+]c was detected at as low as 10(-12) M and increased in a dose-dependent manner. 1-34hPTH increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PTH mobilizes calcium from an intracellular pool. In line with these observations, 1-34hPTH increased the production of inositol trisphosphate. These results suggest that: (1) PTH activates both cyclic AMP and calcium messenger systems and (2) PTH stimulates glycogenolysis mainly via the calcium messenger system.
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PMID:Calcium rather than cyclic AMP is an intracellular messenger of parathyroid hormone action on glycogen metabolism in isolated rat hepatocytes. 254 64

We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).
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PMID:A case of multiple endocrine neoplasia (MEN) type 1; the immunohistochemical and ultrastructural studies of its tumors and the analysis of hormones in tumor extracts. 256 30

Male patients with recurrent calcium (Ca) urolithiasis (RCU) with idiopathic hypercalciuria (I-HC, n = 12) or normocalciuria (NC, n = 12), and age, sex, and weight-matched controls (C, n = 12) were evaluated before and after a carbohydrate-rich synthetic meal for blood glucose, free fatty acids (FFA), alpha-amino-nitrogen, several glucometabolic hormones and parathyroid hormone (PTH), and urine Ca, phosphate, oxalate, and cyclic adenosine monophosphate (cAMP) levels as well as saturation. Fasting serum Ca was significantly higher and PTH significantly lower in I-HC than in controls, whereas in fasting urine cAMP and phosphate were unchanged. There were only minor differences between fasting blood glucose levels and postprandial glucose tolerance of RCU patients and controls. However, serum insulin was significantly elevated in I-HC versus C, but serum C-peptide, plasma glucagon, and somatostatin levels were comparable in RCU and C. FFA were significantly lower in RCU than C. Postprandial phosphaturia and urinary saturation with Ca-phosphates were significantly higher in RCU versus C, whereas urinary cAMP, pH, and oxalate were similar. We conclude that: (1) in RCU patients some postabsorptive steps in glucose metabolism may be abnormal; (2) those with I-HC have enhanced postprandial Ca and phosphate excretion concomitantly with disordered insulin metabolism; and (3) RCU patients may suffer from a postprandial renal phosphate leak, which may make their urine more lithogenic.
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PMID:Blood levels of glucometabolic hormones and urinary saturation with stone forming phases after an oral test meal in male patients with recurrent idiopathic calcium urolithiasis and in healthy controls. 257 28

That the adaptation of the kidney to the acid-base status may be controlled by peptide hormones is considered. In the proximal tubule parathyroid hormone (PTH) inhibits reabsorption of both bicarbonate and phosphate. The former effect is compensated for by an increase in bicarbonate absorption in Henle's loop, and the latter effect serves to augment phosphate concentration in the distal tubular fluid, which stimulates proton secretion in collecting ducts, the net effect of PTH administration being an enhancement of urinary acidification. In the thick ascending limb, both antidiuretic hormone (ADH) and glucagon inhibit bicarbonate absorption. In distal and cortical collecting tubules ADH stimulates net bicarbonate absorption and glucagon net bicarbonate secretion, which results in stimulation and inhibition of final urine acidification, respectively. Acute acid loading stimulates endogenous PTH secretion, which, by enhancing urinary acidification, constitutes a homeostatic response of the parathyroid glands. The major effects of ADH on urinary acidification serve at least to counterbalance disturbing consequences on urinary ammonia excretion of physiological variations in the urinary flow rate. The physiological significance of the effects of glucagon is unclear at present. Thus other peptide hormones may add to PTH and corticosteroid hormones to modulate urinary acidification, which leads to the concept of a pluri-hormonal control of acid-base balance.
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PMID:Peptide hormone effects on urinary acidification and acid-base balance: PTH, ADH, and glucagon. 266 May 94

The effect of vasoactive intestinal peptide (VIP) and related peptides [glucagon, secretin, PHI 1-27 (peptide with N-terminal histidine and C-terminal isoleucine)] on renal adenylate cyclase (AC) has been determined in several species. The largest stimulation (4.1 +/- 0.5-fold basal) of AC by 1 mumol.l-1 VIP was observed in feline cortical plasma membranes. In rabbit and guinea-pig, VIP increased AC activity 1.5 +/- 0.3- and 1.8 +/- 0.3-fold respectively but glucagon had no such action. Conversely in the rat glucagon stimulated AC some 3-fold over basal activity whereas VIP had little effect. In dog, cat and mouse both peptides were effective in increasing AC activity. For cat, half-maximal stimulation of cortical plasma membrane AC by VIP was seen at 27.0 +/- 9.0 nmol.l-1 (SE N = 9 animals). VIP also increased AC activity in both outer (red) and inner (white) medulla. In feline cortical membranes VIP and PTH (parathyroid hormone) when added in combination were fully additive. However for VIP and glucagon in combination there was no cumulative increase in AC activity, indeed the resultant activity was less than that attained by VIP alone. The VIP analogue (4Cl-D-Phe6Leu17)VIP at 10 mumol.l-1 produced a right shift in the VIP-dose response curve and increased the EC50 from 17.2 +/- 5.8 nmol.l-1 to 132.0 +/- 22.2 nmol..-1 VIP (SE N = 4). There was no reduction in the maximum response elicited by VIP consistent with a competitive type of antagonism by this analogue. PHI-stimulated AC was also reduced by (4Cl-D-Phe6Leu17)VIP resulting in a similar right shift in the dose response curve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasoactive intestinal peptide stimulation of renal adenylate cyclase and antagonism by (4Cl-D-Phe6Leu17)VIP. 275 76

Using a biologically active radioligand, [Tyr(125I)10]VIP, we have identified and characterized receptors for vasoactive intestinal peptide (VIP) on membranes prepared from the rat superior mesenteric artery and bovine coronary arteries. Binding was specific, saturable, reversible and dependent on time and temperature. Scatchard analysis suggested the presence of a high and a low affinity binding site in each arterial system with the following binding constants: the rat mesenteric artery, KD = 0.22 +/- 0.02 and 13.6 +/- 7.8 nM (corresponding maximum number of binding sites, RO = 606 +/- 44 fmol/mg protein and 2.1 +/- 0.2 pmol/mg protein); bovine circumflex coronary artery, KD = 0.10 +/- 0.01 and 37.8 +/- 16.1 nM (corresponding RO = 369 +/- 65 fmol/mg protein and 2.0 +/- 0.7 pmol/mg protein); bovine left and right descending coronary arteries, KD = 0.12 +/- 0.03 and 21.3 +/- 6.4 nM (corresponding RO = 472 +/- 7 fmol/mg protein and 2.2 +/- 0.3 pmol/mg protein). The arterial VIP receptors did not recognize secretin, glucagon, apamin or bovine parathyroid hormone, and had reduced affinity for PHI, PHM and growth hormone releasing factors (GRF). These recognition properties were, by and large, similar to those seen in the bovine cerebral arteries although a between-species heterogeneity of recognition function could be deduced from the differences in the competitive binding of rat and bovine vascular VIP receptors with the corresponding species-specific GRFs.
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PMID:VIP receptors in mesenteric and coronary arteries: a radioligand binding study. 282 20

A procedure was developed for isolating thick ascending limb cells from either the outer medulla or the inner cortex from rabbit kidneys. Dispersed cells derived from the medulla or cortex were incubated with goat anti-human uromucoid (Tamm-Horsfall glycoprotein) serum, washed, and applied to culture dishes coated with affinity-purified anti-goat immunoglobulin G. Nonadherent cells were removed by washing. Routinely, 10(6) or 7 X 10(4) adherent cells were obtained per gram of rabbit outer medulla or inner cortex, respectively. Greater than 97% of the adherent cells stained for Tamm-Horsfall antigen, and examination of freshly isolated cells by transmission electron microscopy established that they had morphological properties expected for thick limb cells. Freshly isolated medullary thick limb (MTALH) cells consistently accumulated cAMP in response to arginine vasopressin (AVP), thyrocalcitonin, prostaglandin E2 (PGE2), and glucagon. PGE2, thyrocalcitonin, parathyroid hormone, and AVP, but not isoproterenol or glucagon, reproducibly stimulated cAMP accumulation in freshly isolated cortical thick limb (CTALH) cells. MTALH cells produced immunoreactive PGE2 when incubated with 10 microM arachidonic acid. In summary, large numbers of highly purified and hormonally responsive rabbit MTALH and CTALH cells can be obtained by immunodissection using commercially available antibody preparations. Because the Tamm-Horsfall antigen is present as an extracellular determinant on thick ascending limb epithelia from many species, this general approach likely can be used to isolate CTALH and MTALH cells from most mammalian kidneys.
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PMID:Immunodissection of cortical and medullary thick ascending limb cells from rabbit kidney. 284 12

A transcriptional cAMP-responsive enhancer element (CRE) consisting of the 8-base pair (bp) palindrome, 5' TGACGTCA 3', is found in several eukaryotic genes. We analyzed the effects on gene transcription of point mutations within the CRE, the influence of the bases surrounding the CRE, and the requirements for transcriptional synergism of tandemly repeated CREs. When inserted as an oligonucleotide with restriction enzyme linker sites, the 8-bp CRE itself is as active in conferring cAMP responsivity on an enhancerless chloramphenicol acetyltransferase reporter plasmid as is a single copy of the choriogonadotropin alpha (CG alpha), twice repeated 18-bp sequence containing the CRE. Point mutations in the first (T to A), fourth (C to G), or eighth (A to T) positions of the CRE, when contained within the CG alpha 18-bp sequence, each inhibited transcriptional activity greater than 90%. However, the identical eighth position A to T mutation occurs in the cAMP-responsive sequence of the vasoactive intestinal peptide (VIP) gene, and that mutant sequence in the context of the adjacent bases of the native VIP sequence is maximally cAMP responsive when inserted in the reporter plasmid. The substantially reduced activity of the core 8-bp CRE when synthesized as a cassette including the adjacent bases of the rat glucagon or bovine parathyroid hormone gene further emphasizes the restrictive influence of particular surrounding sequences. Active oligonucleotides containing the 8-bp palindrome and different but equally permissive contexts have comparable properties in transfected reporter genes and gel mobility-shift assays. The pair of tandemly repeated 18-bp elements containing the CRE in the CG alpha gene synergistically stimulate transcription either with paired native CREs or when one native CRE is paired with one mutant CRE, suggesting the presence of cooperative interactions. Tandem insertion of more than two 18-bp sequences, or insertion of additional sequences between the two CREs, inhibits transcription. These observations indicate that the contexts of the bases adjacent to CREs exert profound influences on the transcriptional activities mediated by the cAMP-responsive elements.
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PMID:Structural determinants for transcriptional activation by cAMP-responsive DNA elements. 284 37

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes. 285 73

Mouse-Chinese hamster hybrids segregating mouse chromosomes were analyzed by Southern hybridization techniques to map the genes for somatostatin (Smst), glucagon (Gcg), calcitonin (Calc), and parathyroid hormone (Pth). The mouse gene for somatostatin, detected on a 20-kb EcoRI fragment, is located on mouse chromosome 16. Glucagon cDNA hybridized to a 14-kb EcoRI fragment residing on chromosome 2. Calcitonin and parathyroid hormone genes, detected on 7.8-kb HindIII and 6.0-kb BamHI fragments, respectively, were on mouse chromosome 7. The calcitonin and parathyroid hormone genes appear to be part of a larger linkage group which has been conserved in mouse and man.
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PMID:Mapping polypeptide hormone genes in the mouse: somatostatin, glucagon, calcitonin, and parathyroid hormone. 288 56


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