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)

Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.
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PMID:Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex. 22 Aug 84

Variables of calcium metabolism were measured in 11 patients with clearly documented acute pancreatitis. Total and ionized calcium levels were either low or in the low-normal range as were phosphorus and total magnesium levels. Parathyroid hormone levels were high, and there was a significant inverse correlation with ionized calcium. Gastrin levels were normal, calcitonin values were uniformly below the detection limit of the assay, and pancreatic glucagon levels were elevated. The hypocalcemia of acute pancreatitis was probably not caused by abnormalities of glucagon, calcitonin, or gastrin secretion. Furthermore, parathyroid hormone secretion was apparently not impaired. Hypomagnesemia possibly played a minor role. This study suggests that the hypocalcemia of acute pancreatitis is secondary to extraskeletal calcium sequestration or an as yet unidentified defect of bone metabolism, or both.
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PMID:The hypocalcemia of acute pancreatitis. 114 52

The mammalian renal thick ascending limb of Henle (TAL) reabsorbs approximately 55% of the filtered magnesium; accordingly, it is the major segment involved in control of renal Mg balance. This review discusses recent evidence for passive and active transport of Mg through the paracellular and transcellular pathways of the TAL, respectively. The properties of these pathways provide a basis for understanding the factors influencing magnesium reabsorption and hormonal controls regulating Mg balance. Normally, Mg absorption is load dependent, whether delivery is altered by increasing luminal Mg concentration or increasing the flow rate into the thick ascending limb. In contrast to the luminal concentration, elevation of peritubular (plasma) Mg and Ca inhibit divalent cation absorption by mechanisms that are not entirely clear. Magnesium reabsorption in the TAL is also closely associated with NaCl absorption so that factors that influence NaCl also affect magnesium. Magnesium deficiency results in a specific and apparently intrinsic cellular adaptation to increase Mg absorption in the TAL. Our greatest understanding of hormonal controls for Mg absorption have come from recent studies using a "hormone deprived" animal model. Parathyroid hormone, calcitonin, glucagon, and antidiuretic hormone act through a common second messenger, adenosine 3',5'-cyclic monophosphate, to limit Mg excretion by enhancing active Mg transport in the TAL. The integrated actions of these hormones and possibly others provide a sensitive means of control. Clearly, recent observations, using in vivo and in vitro microperfusion studies, have altered our thinking of TAL function and indicate that Mg transport is sensitively and specifically controlled within this segment.
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PMID:Control of magnesium transport in the thick ascending limb. 264 45

Chlorpromazine (3 x 10(-4)M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 x 10(-4)M F(-)-stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F(-)-stimulated cyclase activity of thyroid. Na(+)- K(+)-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.
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PMID:Inhibition of hormone-sensitive adenyl cyclase by phenothiazines. 431

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

Parathyroid hormone (PTH) binds to its receptor (PTH 1 receptor, PTH1R) and activates multiple pathways. The PTH1R, a class b GPCR, contains consensus calmodulin-binding motifs. The PTH1R cytoplasmic tail interacts with calmodulin in a calcium-dependent manner via the basic 1-5-8-14 motif. Calcium-dependent calmodulin interactions with the cytoplasmic tails of receptors for PTH 2, vasoactive intestinal peptide, pituitary adenylate cyclase activating peptide, corticotropin releasing hormone, calcitonin, and the glucagon-like peptides 1 and 2 are demonstrated. The cytoplasmic tails of the secretin receptor and the growth hormone releasing hormone receptor either interact poorly or not at all with calmodulin, respectively. Fluphenazine, a calmodulin antagonist, enhances PTH-mediated accumulation of total inositol phosphates, suggesting that calmodulin regulates signaling via phospholipase C.
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PMID:Calmodulin interacts with the cytoplasmic tails of the parathyroid hormone 1 receptor and a sub-set of class b G-protein coupled receptors. 1567 Aug 50

Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-A structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer alpha-beta-betaalpha fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.
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PMID:Molecular recognition of parathyroid hormone by its G protein-coupled receptor. 1837 60

Glucose-mediated energy production in central nervous system(CNS) reduces in the elderly. The reduction is also observed in young patients with diabetes mellitus(DM). Deviated endocrinological function is observed in both the elderly and young patients with DM. The deviation is characterized by mechanism of adaptation to the insufficient energy production in CNS. The decrease of glucose-mediated energy production is accelerated by decrease of the activity of growth hormone-insulin-like growth factor 1 axis and of conversion of thyroxine to triiodothyronine. These decreases are suitable for adaptation to the insufficient CNS activity induced by energy deficiency. Glucagon- and catecholamine-induced increases in plasma glucose level contribute to increase energy production. Parathyroid hormone action is activated in the elderly, which contributes to the inhibition of excess signal transduction in energy-deficient CNS. These deviations are considered as adaptations to the energy deficiency observed in aged patients with DM.
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PMID:[Endocrinological aspects of diabetes mellitus in the elderly]. 2439 63

Hormones within very low levels regulate and control the activity of specific cells and organs of the human body. Hormone imbalance can cause many diseases. Therefore, hormone detection tools have been developed, particularly over the last decade. Peptide hormones have a short half-life, so it is important to detect them within a short time. In this study, we report two types of peptide hormone sensors using human hormone receptor-carrying nanovesicles and graphene field-effect transistors (FETs). Parathyroid hormone (PTH) and glucagon (GCG) are peptide hormones present in human blood that act as ligands to G protein-coupled receptors (GPCRs). In this paper, the parathyroid hormone receptor (PTHR) and the glucagon receptor (GCGR) were expressed in human embryonic kidney-293 (HEK-293) cells, and were constructed as nanovesicles carrying the respective receptors. They were then immobilized onto graphene-based FETs. The two hormone sensors developed were able to detect each target hormone with high sensitivity (ca. 100 fM of PTH and 1 pM of GCG). Also, the sensors accurately recognized target hormones among different types of peptide hormones. In the development of hormone detection tools, this approach, using human hormone receptor-carrying nanovesicles and graphene FETs, offers the possibility of detecting very low concentrations of hormones in real-time.
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PMID:Peptide hormone sensors using human hormone receptor-carrying nanovesicles and graphene FETs. 3194 24