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 aging kidney suffers reduction both in mass and in glomerular filtration rate. These changes may be totally or partially due to atherosclerosis and hypertension, which reduce renal blood flow. Superimposed on these processes, and perhaps responsible for primary loss of renal mass irrespective of renal vascular disease, is glomerular damage and involution that is a consequence of adaptive increases in glomerular perfusion pressure that occurs as the number of nephrons decline with age. The data available at this time do not allow us to distinguish between these two potential mechanisms of renal senescence. The decline in GFR is in turn responsible for reduced renal acidification and the reduced renal clearance of drugs that are normally removed by the kidney. Certain renal functions, however, are depressed to a greater extent than is GFR. Both the ability to maximally dilute the urine and to maximally concentrate it are controlled by serum ADH concentrations and by the action of that hormone on the collecting duct. Aged rats do not maximally secrete ADH under conditions of dehydration and the effect of ADH on the kidney is also attenuated. Elderly humans also cannot maximally suppress ADH secretion when serum osmolality is reduced. Likewise, the renin-angiotensin-aldosterone axis is poorly responsive to volume depletion in aging subjects. As a result, elderly individuals cannot maximally retain sodium under conditions of plasma volume contraction out of proportion to reduction in GFR. The kidney is the site of vitamin D1 hydroxylation. Hydroxylation of vitamin D is reduced out of proportion to any reduction in GFR in the rat. There are no data as yet available on the effect of aging and the production of erythropoietin, a principal regulator of red blood cell mass. Neither are there data available on changes that might occur with advancing age in the ability of the aging kidney to metabolize various hormones, such as parathyroid hormone, glucagon, and insulin. The mechanisms and the full biochemical and physiologic consequences of renal senescence remain to be fully elucidated.
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PMID:The aging kidney. 391

We evaluated the effects of human calcitonin (hCT) on electrolyte excretion in hormone-deprived rats, that is, in the absence of endogenous parathyroid hormone, antidiuretic hormone, thyrocalcitonin and glucagon, the effects of which might have interfered with those of exogenous calcitonin. Plasma hCT levels, measured by radioimmunoassay, varied from 0 to 32 ng/ml. In these rats, hCT decreased magnesium (Mg) and calcium (Ca) excretion in a dose-dependent fashion. Maximal decreases were observed for hCT plasma concentrations comprised between 3 and 5 ng/ml, and persisted at the highest doses. Sodium, potassium, water, and total solute excretions were constant in the calcitonin concentration range explored. The same was observed for phosphate, except that slight but significant phosphaturia was elicited by the highest doses. Calcium and phosphate infusions to attenuate the fall in plasma Ca and phosphate concentration subsequent to hCT infusion, did not alter the hormonal effect on Ca and Mg excretion. hCT can therefore directly modulate Mg and Ca reabsorption by the kidney at plasma concentrations within the physiological range. The maximal effects on Mg and Ca reabsorption were obtained at plasma concentrations which are generally reached after maximal stimulation of endogenous calcitonin secretion. It is suggested that in rats, endogenous secretion of calcitonin stimulates Ca and Mg renal reabsorption without modification of sodium and phosphate excretion.
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PMID:Modulation by calcitonin of magnesium and calcium urinary excretion in the rat. 399 91

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on the handling of water and electrolytes by the juxtamedullary nephrons were studied on rats with reduced circulating levels of antidiuretic hormone (ADH), parathyroid hormone, calcitonin, and glucagon, all of which stimulate the adenylate cyclase system of the thick ascending limb and the distal tubule. In such hormone-deprived rats and in hormone-deprived + dDAVP rats, the concentration of Na, Cl, and total solutes was lower in the ascending than in the descending limbs, whereas the inulin concentration was similar at both sites. dDAVP did not alter the fraction of NaCl remaining in the thin limbs, but tended to reduce that of Mg and Ca. On the other hand, dDAVP significantly increased the fraction of filtered K remaining from 65.8 +/- 5.2 to 107.3 +/- 15.8%. A direct correlation was observed between the fraction of filtered K remaining at the tip of the juxtamedullary loops and the fractional excretion rate of K in urine. Since dDAVP enhances distal K net secretion, as previously shown in our laboratory, these results indicate that the medullary recycling of K from nephron terminal segments to Henle's loop of juxtamedullary nephrons is stimulated by this peptide.
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PMID:Effects of dDAVP on rat juxtamedullary nephrons: stimulation of medullary K recycling. 402 56

Two biologically active, 34 amino acid fragments of parathyroid hormone interact with dimyristoylphosphatidylcholine to form lipoprotein particles. In the lipid-bound form these parathyroid hormone peptides exhibit an increased amount of folded secondary structure and the tryptophan residue of [Nle8, Nle18, Tyr34] b PTH (1-34) amide appears to become buried in a more hydrophobic environment. The lipoprotein particle which is formed has dimensions of approximately 65 X 7 nm but aggregates to larger structures with increasing temperature. Above the phase transition of the phospholipid the peptides no longer affect the morphology of the lipid and the spectral properties of the peptide are not perturbed by the lipid. This is similar to the behavior of glucagon with dimyristoylphatidylcholine. The results indicate that several nonhomologous peptide hormones have common features which allow them to fold into an amphipathic helix and solubilize phospholipid.
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PMID:Formation of water-soluble complex between the 1-34 fragment of parathyroid hormone and dimyristoylphosphatidylcholine. 403 Feb 17

The interaction of glucagon, human parathyroid hormone-(1-34)-peptide and salmon calcitonin with dimyristoylphosphatidylglycerol (DMPG) and with dimyristoylphosphatidylcholine (DMPC) was studied as a function of pH and temperature. The effect of lipid on the secondary structure of the peptide was assessed by circular dichroism and the effect of the peptide on the phase transition properties of the lipid was studied using differential scanning calorimetry. Some peptides interact more strongly with anionic than with zwitterionic phospholipids. This does not require an overall positive charge on the peptide. Increased thermal stability is observed in complexes formed between cationic peptides and anionic lipids. Particularly marked effects of glucagon and human parathyroid hormone-(1-34)-peptide on the phase transition properties of DMPG at pH 5 have been observed. The transition temperature is raised over 10 degrees C at a lipid/peptide molar ratio of less than 30:1 and the transition enthalpy is increased over 2-fold. These effects do not occur with any basic peptide and were not observed with metorphinamide, molluscan cardioexcitatory neuropeptide or myelin basic protein. The results demonstrate that certain peptides can affect the phase transition properties of lipids in a manner similar to divalent cations. The overall hydrophobicities of these peptides can be evaluated by their partitioning between aqueous and organic solvents. None of the above three peptide hormones partition into the organic phase. However, a closely related peptide, human calcitonin, does exhibit substantial partitioning into the organic phase. Nevertheless, human calcitonin has a weaker interaction with both DMPC and DMPG than does salmon calcitonin. The effects of human calcitonin on the phase transition of DMPC are qualitatively different from those of salmon calcitonin in that the human form more readily eliminates the pretransition but causes less change in the main transition. Like overall charge, overall hydrophobicity is not an overwhelming factor in determining the ability of peptides to interact with phospholipids but rather more specific interactions are required for strong complexes to form.
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PMID:A comparison of the interaction of glucagon, human parathyroid hormone-(1-34)-peptide and calcitonin with dimyristoylphosphatidylglycerol and with dimyristoylphosphatidylcholine. 409 81

Properties of adenyl cyclase of normal adrenals and of a corticosterone-producing adrenal cancer of the rat have been compared. Enzyme activity was found in all particulate fractions of both tissues. The cyclase of the tumor as well as of the adrenals was stimulated by adrenocorticotropic hormone (ACTH) over similar concentration ranges. Unexpectedly, the tumor enzyme was also stimulated by epinephrine, norepinephrine, and thyroid-stimulating hormone (TSH). These hormones produced a dose-related effect over a concentration span that was comparable with that for ACTH. The tumor cyclase was not responsive to angiotensin Il, vasopressin, glucagon, insulin, growth hormone, parathyroid hormone, and thyrocalcitonin. ACTH was the only hormonal preparation that stimulated normal adrenal cyclase. These findings are compatible either with the possibility that the adenyl cyclase receptor of the tumor has undergone structural alteration with a consequent loss of specificity for ACTH or with the possibility that the tumor possesses several cyclase regulatory receptors.
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PMID:Abnormal hormone responses of an adrenocortical cancer adenyl cyclase. 432 11

Biologically active (125)I-labeled bovine parathyroid hormone (prepared by electrolytic iodination) and its synthetic NH(2)-terminal (1-34) biologically active fragment bound rapidly and specifically to a purified plasma membrane preparation from bovine renal cortex. Binding of labeled intact hormone or labeled NH(2)-terminal (1-34) peptide was inhibited competitively by unlabeled (1-34) peptide in the same range of concentrations that activated renal cortical 3':5'-adenylate cyclase (EC 4.6.1.1) in these membranes. The concentrations of synthetic (1-34) peptide for half-maximal inhibition of binding of labeled hormone as well as half-maximal activation of the enzyme were about 0.6 muM (2.5 mug/ml). Therefore it is likely that the binding activity studied represents a physiologically important renal receptor for parathyroid hormone. Biologically inactive (oxidized) forms of parathyroid hormone and (1-34) NH(2)-terminal peptide as well as calcitonin, glucagon, insulin, and epinephrine failed to competitively inhibit the binding of labeled (1-34) parathyroid hormone or activate adenylate cyclase in the renal cortical membrane preparation. Observations with the NH(2)-terminal (1-34) biologically active fragment of parathyroid hormone suggest that the COOH-terminal region of the molecule is not required for receptor binding.
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PMID:Parathyroid hormone receptors of renal cortex: specific binding of biologically active, 125I-labeled hormone and relationship to adenylate cyclase activation. 436 30

1. The effect of iodination on the distribution of peptide hormones into the aqueous two-phase dextran-polyethylene glycol system and on the solubility of these hormones in aqueous polyethylene glycol and in water was assessed. Hormones that were studied included insulin, glucagon and parathyroid hormone. 2. The partition coefficient of native insulin in the dextran-polyethylene glycol system showed a minimum (about 1) near the isoelectric point of the hormone (pH 5). Partial iodination of insulin (one atom per molecule) caused little change in the distribution of the hormone. More extensive iodination markedly decreased the partition coefficient in the region of the isoelectric point and displaced the pH value at which the partition coefficient was a minimum towards lower values. 3. The solubility of native insulin in aqueous polyethylene glycol and in water showed a pH-dependence similar to that observed for the distribution in the dextran-polyethylene glycol system. Iodination of insulin decreased the solubility of the hormone in polyethylene glycol and in water in parallel, and decreased the pH value at which solubility was a minimum. The changes in solubility correlated with the degree of iodination and accounted for the changes in distribution observed at high concentrations of insulin. 4. Comparable effects of iodination on distribution and solubility were also observed with glucagon. 5. At concentrations of insulin below its maximum solubility, serum proteins caused a decrease in the partition coefficient of iodinated hormone, but not of native hormone. These effects correlated with the degree of iodination and resulted from a co-precipitation of iodinated insulin with serum proteins.
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PMID:Effects of iodination on the distribution of peptide hormones in aqueous two-phase polymer systems. 446 59

Glucagon, infused intravenously into fasting, well-hydrated, normal men in doses of 25-200 ng/kg per min, induced up to 30-fold increases in both plasma and urinary cyclic AMP. Cyclic GMP levels were unaffected by glucagon. Simultaneous cyclic AMP and inulin clearance studies demonstrated that the glucagon-induced increase in urinary cyclic AMP was entirely due to glomerular filtration of the elevated plasma levels of the nucleotide. The cyclic AMP response to glucagon was not mediated by parathyroid hormone or epinephrine, and trypsintreated glucagon was completely inactive. The perfused rat liver released cyclic AMP into the perfusate in response to glucagon, indicating that the liver is a possible source of the cyclic AMP entering the extracellular fluids in response to glucagon in vivo.
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PMID:Effects of glucagon on adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in human plasma and urine. 548 Aug 50

The effects of parathyroid hormone (PTH) on plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) levels were studied in normal subjects. Under basal conditions normal adults have plasma concentrations of cyclic AMP ranging from 10 to 25 nmoles/liter and excrete from 1.5 to 5 mumoles of cyclic AMP per g of urinary creatinine. About one-half to two-thirds of the cyclic AMP excreted in the urine is derived from the plasma by glomerular filtration, and the remainder is produced by the kidney. Renal production of cyclic AMP is partly under the control of PTH. It can be suppressed by infusions of calcium and stimulated by infusions of the calcium chelating agent, EDTA. Infusions of PTH in doses up to 10 mU/kg per min were associated with dose-related increases both in urinary cyclic AMP and phosphate. Infusions of PTH in doses ranging from 20 to 80 mU/kg per min did not lead to any further increase in phosphaturia but did lead to further marked increases in urinary cyclic AMP. A modest increase in plasma cyclic AMP was noted when PTH was infused at 40 mU/kg per min. Anephric patients failed to show appreciable increases in plasma cyclic AMP in response to large doses of PTH but did show expected increases in response to glucagon. Surgical removal of parathyroid adenomas from nine patients with primary hyperparathyroidism was invariably followed by a decrease in urinary cyclic AMP, PTH, in large doses, and calcium infusion produced up to 2-fold increases in the other known naturally occurring cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP).
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PMID:Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man. 548 Aug 62


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