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)

Adrenal insufficiency is associated with an impairment of kidney diluting and concentrating ability, defects that may result from alterations of vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The purpose of this study were 1) to localize the sites of decreased vasopressin-stimulated adenylate cyclase (AC) activity along the nephron of adrenalectomized rats; 2) to determine whether the response of AC to other hormones is altered by adrenalectomy; 3) to evaluate whether changes in AC are due to the deficiency in mineralocorticoids and/or glucocorticoids; and 4) to characterize the mechanism of action of corticosteroids on the AC system. Results indicate that adrenalectomy reduced AC stimulation by vasopressin, glucagon, and calcitonin in the thick ascending limb, whereas only the response to vasopressin decreased in the collecting tubule. Glucocorticoid administration curtailed adrenalectomy-induced alterations of AC in the thick ascending limb, whereas that in the collecting tubule was prevented by mineralocorticoids. Adrenalectomy did not alter forskolin-stimulated AC, whereas it decreased responses to aluminum fluoride and cholera toxin. Finally, alterations of fluoride- and cholera toxin-stimulated AC were prevented by glucocorticoid and mineralocorticoid repletion in the thick ascending limb and collecting tubule, respectively.
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PMID:Gluco- and mineralocorticoids control adenylate cyclase in specific nephron segments. 215 44

Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.
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PMID:Consequences of phosphate imbalance. 306 Jan 61

In order to test the safety of glucagon (GG), the immunogenicity of GG was studied in rabbits and guinea pigs. Any sensitization, as revealed by anaphylactic shock, Arthus reaction, passive cutaneous anaphylaxis (PCA) or radioimmunoassay, was not demonstrated in animals immunized with GG alone. The anti-GG antibodies were detected by PCA and radioimmunoassay in two of the five animals immunized with GG mixed with Freund's complete adjuvant. Anti-GG IgE antibody production in mice was found in one of the ten mice given 570 micrograms and three of the six mice given 1,000 micrograms of GG with aluminum hydroxide gel (Alum), but other doses of GG with Alum produced no IgE antibody. These results indicate that the antigenicity of GG is very weak.
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PMID:Studies on the antigenicity of glucagon. 623 Jul 59

Blood-borne insulin is known to cross the blood-brain barrier (BBB) where it can act as a satiety peptide. We examined in mice the pharmacokinetics and characteristics of such passage by multiple-time regression analysis. The unidirectional influx constant (Ki) of human insulin radioactively labeled with iodine (I-Ins) ranged from 0.87 to 1.7 microliters/g-min. The transport of I-Ins was inhibited almost 50% by 0.1 micrograms/mouse of unlabeled human insulin, a dose that had no effect on serum glucose. Similar results were found with rat insulin. The results with self-inhibition suggest that any hemoencephalic signal transmitted by the blood to brain transport of insulin is independent of the effects of insulin on glucose. The transport of I-Ins was altered by aluminum but not by administration of tyrosine, verapamil, or leptin, indicating independence from amino acid transport, the p-glycoprotein system, a slow calcium channel, or leptin transport. By contrast with insulin, enzyme degradation limited the uptake and accumulation by brain of intravenously injected, radioactively labeled glucagon and glucagon-like peptide. In conclusion, these results are consistent with the view that insulin can affect satiety and related behaviors independently of its peripheral effects by crossing the BBB to act within the brain.
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PMID:Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. 939 46

Aluminium phosphide (AlP) is used to protect stored grains from rodents. It produces phosphine gas (PH3), a mitochondrial poison thought to cause toxicity by blocking the cytochrome c oxidase enzyme and inhibiting oxidative phosphorylation, which results in cell death. AlP poisoning has a high mortality rate among humans due to the rapid onset of cardiogenic shock and metabolic acidosis, despite aggressive treatment. We report a 21-year-old male who was referred to the Afzalipour Hospital, Kerman, Iran, in 2015 after having intentionally ingested a 3 g AlP tablet. He was successfully treated with crystalloid fluids, vasopressors, sodium bicarbonate, digoxin, glucagon and antioxidant agents and was discharged from the hospital six days after admission in good clinical condition. For the treatment of AlP poisoning, the combination of glucagon and digoxin with antioxidant agents should be considered. However, evaluation of further cases is necessary to optimise treatment protocols.
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PMID:Treatment of Aluminium Phosphide Poisoning with a Combination of Intravenous Glucagon, Digoxin and Antioxidant Agents. 2760 17