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)

In the submitted review the author pays attention to mechanisms of control of insulin secretion and the mutual interaction of other messengers (cAMP, calcium and inisitol triphosphate) with special attention to the calcium signal which plays a most important role in the stimulation of the excitable B cell. The trigger of the two-stage insulin secretion is cyclic accumulation of calcium in the cytosol of the B cell and the mutual harmony between calcium of the intra- and extracellular compartment. In the early stage of insulin secretion in particular the intracellular compartment is the source of calcium; from there the ion is released due to the action of inositol triphosphate (IP3) activated by phospholipase C. Calcium of the extracellular compartment is mobilized also in the early secretory stage by opening of the depolarization-dependent calcium channels, it plays, however, a more important part during the second stage. Activation of the other messengers, incl. the calcium signal, depends on the type of secretagogue stimulus. During systemic changes of calcium homeostasis in vivo the calcium signal of the B cell is activated or inhibited in different ways. In the course of hypercalcaemia, in particular if acute, the direct influence of calcium ions on insulin secretion is modulated by further factors, e.g. somatostatin, calcitonin, cholecystokinin, glucagon, adrenocortical hormones, opioids and other substances released into the blood stream. In chronic hypercalcaemia which is the result of primary hyperparathyroidism or vitamin D intoxication the action of calcium on the metabolic and hormonal response is enhanced by the ionophoretic action of parathormone or active vitamin D metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The calcium signal in the regulation of insulin secretion]. 269 62

The aetiology of the rise in plasma calbindin-D9K (vitamin D-induced calcium-binding protein; CaBP), following insulin-induced hypoglycaemia, was studied in the pig. ACTH led to a rise in plasma concentrations of both CaBP and cortisol. Metyrapone, which blocks cortisol synthesis, abolished the increases in plasma concentrations of CaBP and cortisol normally observed in response to insulin-induced hypoglycaemia. However, there was no significant rise in plasma concentrations of CaBP in response to pharmacological or physiological doses of cortisol. Injection of clonidine, an alpha 2-adrenergic agonist, led to a rise in plasma concentrations of CaBP, whereas phenylephrine, an alpha 1-adrenergic agonist, tended to exert an inhibitory effect. Also, administration of phentolamine (an alpha-adrenergic blocker) before injection of insulin abolished the usual increase in plasma concentrations of CaBP, whereas propranolol (a beta-adrenergic blocker) enhanced the normal increase in plasma concentrations of CaBP in response to insulin-induced hypoglycaemia. Isoproterenol, a beta-adrenergic agonist, was without effect on plasma CaBP. Neither GH nor glucagon appear to be involved in the rise in plasma CaBP following insulin-induced hypoglycaemia. Although atropine abolished the effect of acute hypoglycaemia on plasma CaBP, carbamylcholine was without effect on plasma CaBP concentration. It is concluded that the increases in plasma CaBP induced by either ACTH or alpha 2-adrenergic stimulation may be interrelated since the administration of ACTH can lead to raised plasma concentrations of catecholamines.
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PMID:Endocrine control of plasma concentrations of calcium-binding protein in the pig. 288 89

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 addition to direct toxic effects on endocrine organs chronic alcohol intake affects regulation of endocrine systems by disturbed liver function. As a result in patients with alcohol-induced liver cirrhosis gonadal axis is characterized by low total and free testosterone, elevated estradiol. LH, FSH, and sexual hormone binding globulin and an enhanced conversion of testosterone to estradiol. Prolactin also is found to be elevated. The thyrotropic axis is characterised by low T3- und T4- as well as elevated rT3-values and normal TSH. STH is elevated, while somatomedin C is decreased. The corticotropic axis may show an abolished circadian rhythm, a negative Dexamethasone-test, low transcortin and elevated free cortisol levels. The disturbance of the calcitropic axis leads to osteoporosis and osteomalacia, due to intestinal hyperparathyroidism and vitamin D malnutrition. In 50% of chronic alcoholics there are elevated insulin and glucagon values and a pathological glucose tolerance test.
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PMID:[Alcohol and endocrinologic homeostasis]. 306 42

Target cells of 1,25-dihydroxyvitamin D3 were identified by autoradiography in islets from rats of different ages. Nuclei of pancreatic islet cells selectively concentrated 1,25-[3H]dihydroxyvitamin D3 but not 25-[3H]hydroxyvitamin D3 or 24,25-[3H]dihydroxyvitamin D3. Developmental studies of pancreatic islets indicated that target cells, as revealed by significant nuclear concentration of 1,25-[3H]dihydroxyvitamin D3, are present in islet cells of fetal rats. The percentage of islet cells that concentrated 1,25-[3H]dihydroxyvitamin D3 increased from 10 to 15% in the fetus to 60% at 1 day of age. Immunocytochemical staining indicated that insulin-containing cells but not glucagon or somatostatin cells concentrated 1,25-[3H]dihydroxyvitamin D3. Peak uptake of 1,25-[3H]dihydroxyvitamin D3 was calculated to be 400 pmol/mg DNA, with no significant difference in nuclear accumulation between islet cells from neonatal and adult rats or between islets in vivo and isolated islets in vitro. The results of these studies indicate that 1,25-[3H]dihydroxyvitamin D3 target cells are present in islets before pancreatic beta-cells are morphologically or functionally mature; islet beta-cells concentrate 1,25-dihydroxyvitamin D3, but not 25-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3. We conclude that only the 1,25-dihydroxyvitamin D3 metabolite of vitamin D is accumulated by nuclei of developing and mature beta-cells and suggest that 1,25-dihydroxyvitamin D3 plays a role in the maturation of islet beta-cells.
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PMID:1,25-Dihydroxyvitamin D3 target cells in immature pancreatic islets. 330 Mar 66

The effects of subclinical vitamin D deficiency and vitamin D supplementation on oral glucose tolerance and secretion of pancreatic hormones were studied in 10 diphenylhydantoin-treated epileptic patients and 15 geriatric patients. Their mean serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 decreased markedly, but returned to normal within 2 weeks of oral supplementation with 25-hydroxyvitamin D3. The serum concentration of ionized calcium was within the normal range before treatment, and remained unchanged. Serum parathyroid hormone was increased during vitamin D deficiency, but decreased significantly (p less than 0.05) afterwards. In vitamin D-deficient epileptic and geriatric patients, the 2- and 3-h insulin levels after glucose ingestion were increased when compared with control values, and glucagon secretion was not suppressed by glucose. Oral glucose tolerance of both groups of patients did not change after 25-hydroxyvitamin D3 supplementation. Insulin secretion remained unchanged in geriatric patients, but was reduced to normal values in epileptic patients. Glucagon suppressibility by glucose was partly restored after vitamin D supplementation in epileptic patients but not in geriatric patients. In contrast to that observed in severely vitamin D-deficient rats or rabbits, correction of subclinical vitamin D deficiency failed to enhance insulin secretion or to improve glucose tolerance in man.
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PMID:Pancreatic secretion in man with subclinical vitamin D deficiency. 375 30

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

Hypertriglyceridaemia is often observed in patients (1) with chronic renal insufficiency, (2) on haemodialysis and (3) after successful renal transplantation. HDL cholesterol is reduced in all three groups of patients and plasma cholesterol is elevated after renal transplantation. In these three patient groups type IV hyperlipoproteinaemia is found most frequently and after renal transplantation there is a relative increase in the incidence of type II hyperlipoproteinaemia. The role of glucagon resistance and carnitine deficiency in the alteration of fat metabolism seen in patients with chronic renal failure and patients on haemodialysis is discussed. Other factors which may influence fat metabolism in uraemia include calcium and vitamin D status as well as beta adrenergic receptor blocking agents and diuretics. Steroid therapy may be one cause of the hypercholesterolaemia and hypertriglyceridaemia seen after renal transplantation. PHLP lipase activity is reduced in all three groups of patients. In nephrotic syndrome, if hypercholesterolaemia occurs, the HDL cholesterol fraction is increased and thus the cardiovascular risk may be lower than in the three patient group mentioned above.
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PMID:[Alterations of fat metabolism in renal disease - pathogenetic mechanisms (author's transl)]. 612 54

The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D-deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas.
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PMID:Vitamin D deficiency inhibits pancreatic secretion of insulin. 625 Feb 16

Historically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions. Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and prostaglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by beta 1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II. Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified natriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide). Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure. Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion. Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected. The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.
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PMID:Endocrine physiology of electrolyte metabolism. 638 78


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