UNIPROT:P01275 - FACTA Search

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Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracerebroventricular (ICV) injection of carbachol elicits hormonal and metabolic responses similar to moderate stress. In normal dogs, ICV carbachol stimulated marked counterregulatory hormone release, but altered plasma glucose only marginally because the marked increment in glucose production (Ra) was almost matched by the increment of utilization (Rd), even though plasma insulin was unchanged. In alloxan-diabetic dogs, Rd did not match Ra and plasma glucose increased substantially. Since somatostatin octapeptide (ODT8-SS) inhibits some sympathetic mechanisms of the stress response, we explored the extent to which ODT8-SS can alleviate the counterregulatory responses to stress induced by carbachol, and particularly whether it can restore glycemic control in diabetes. ODT8-SS (20 nmol) was ICV-injected (1) in normal dogs (n = 5), and (2) prior to ICV carbachol before (n = 7) and after (n = 6) the induction of alloxan-diabetes. ODT8-SS did not affect basal values, but when administered before ICV carbachol there were no significant increments in plasma epinephrine, cortisol, arginine vasopressin (AVP), insulin, glucose, or lactate. There were significant increases in norepinephrine, glucagon, Ra, Rd, and the glucose metabolic clearance rate (MCR), although they were much smaller than seen previously with ICV carbachol alone. After induction of alloxan-diabetes, Rd and MCR did not change with ICV ODT8-SS and carbachol as in normal dogs, but norepinephrine, epinephrine, glucagon, lactate, plasma glucose, and Ra increased, although with the exception of glucagon these increases were much smaller than seen previously with ICV carbachol alone. ODT8-SS administered before ICV carbachol in normal or diabetic animals resulted in increased free fatty acid (FFA) levels. The increases in glycerol were less than and those in FFA greater than seen previously with ICV carbachol alone. Since ODT8-SS does not alter basal counterregulatory hormone release but suppresses the release during stress, this is a useful probe to analyze some of the metabolic responses to stress. When the response to carbachol from our previous report is compared with the responses to carbachol + ODT8-SS, it is indicated that the stress-related increase in Ra was consistent with stimulation of the sympathetic nervous system, whereas increased Rd is related to an unknown stress-related neuroendocrine mechanism that requires a permissive effect of insulin, since it was not seen in the frankly diabetic animals. We hypothesize that the stress-induced increase in Rd occurs not only in muscle but also in adipocytes, and that the somatostatin-induced attenuation of Rd decreased FFA re-esterification and consequently markedly increased stress-induced FFA release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracerebroventricular administration of somatostatin octapeptide counteracts the hormonal and metabolic responses to stress in normal and diabetic dogs. 791 19

To determine whether renal reserve capacity was preserved in patients with chronic glomerulonephritis with well-preserved kidney function, and how sodium was handled in proximal and distal tubules, 13 healthy control subjects and 13 patients with biopsy-verified chronic glomerulonephritis were studied before and during a continuous 120-min amino-acid infusion. Glomerular filtration rate (GFR), renal plasma flow (RPF), and tubular function evaluated by the lithium clearance method, were determined during six clearance periods of 30 min each. Plasma concentrations of angiotensin II, atrial natriuretic peptide (ANP), aldosterone, arginine vasopressin (AVP), glucagon, amino acid and serum osmolality were determined before, 60, and 120 min after infusion. GFR and RPF increased about 10% in both groups; filtration fraction (FF) was unchanged. Proximal tubular reabsorption of sodium and water decreased, and distal tubular reabsorption of sodium and water increased, and thus the net excretion of sodium and water was unchanged. Angiotensin II and aldosterone were reduced in control subjects, but not in the patients. ANP and glucagon increased equally in both groups. Most amino acids increased two- or threefold. It is concluded that renal reserve capacity and glomerulotubular balance are intact in patients with chronic glomerulonephritis with well-preserved renal function, but there is an abnormal lack of suppression of the renin-angiotensin-aldosterone system in response to an amino acid infusion in these patients.
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PMID:Renal haemodynamic changes, renal tubular function, sodium and water homeostatic hormones in patients with chronic glomerulonephritis and in healthy humans after intravenous infusion of amino acids. 809 Mar 30

Expression of Ca2+-inhibitable types V and VI adenylyl cyclases was studied by reverse transcription-polymerase chain reaction in rat renal glomeruli and nephron segments isolated by microdissection. Quantitation of each mRNA was achieved using a mutant cRNA which differed from the wild type by substituting two bases to create a new restriction site in the corresponding cDNA. Type VI mRNA was present all along the nephron but was more abundant in distal than in proximal segments. The expression of type V mRNA was restricted to the glomerulus and to the initial portions of the collecting duct. Expression of the Ca2+-insensitive type IV mRNA studied on the same samples was evidenced only in the glomerulus. The functional relevance of the expression of Ca2+-inhibitable isoforms was studied by measuring cAMP content in the microdissected outer medullary collecting duct which expressed both type V mRNA (2367 +/- 178 molecules/mm tubular length; n = 8) and type VI mRNA (5658 +/- 543 molecules/mm, n = 8). Agents known to increase intracellular Ca2+ in this segment induced a Ca2+-dependent inhibition on either arginine vasopressin- or glucagon-stimulated cAMP level. The characteristics of these inhibitions suggest a functional and differential expression of types V and VI adenylyl cyclases in two different cell types of the rat outer medullary collecting duct.
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PMID:Localization of mRNAs encoding Ca2+-inhibitable adenylyl cyclases along the renal tubule. Functional consequences for regulation of the cAMP content. 870 8

The effects of hypothalamic heating and cooling on thermoregulatory effector activities, lipid and carbohydrate metabolism, insulin, glucagon, thyroxine, arginine vasopressin (AVP) and cortisol were investigated in conscious rabbits and compared with those obtained in the febrile state. The study shows that under control conditions hypothalamic heating lowers, and cooling raises core temperature. Core temperature always rose to similar degrees in response to bacterial lipopolysaccharide (LPS) during an observation time of 150 min, but it started to rise from lower and higher levels, respectively, during hypothalamic heating and cooling. The effects of hypothalamic thermal stimulation on specific thermoregulatory effector activities support the conclusion that, within 60 min after LPS, the hypothalamic warm signal input is reduced relative to the cold signal input. The increase of thyroxine levels following LPS suggests that the elevation of the thermoregulatory setpoint was caused by an increased input of hypothalamic TRH neurons, known to induce the full autonomic pattern of cold defense also in response to non-thermal stimuli. With the exception of an increase of glucagon during hypothalamic cooling at control conditions, hypothalamic thermal stimulation alone did not alter lipid and carbohydrate metabolism, insulin, thyroid hormone, AVP and cortisol secretion. A spontaneous heat loss effector response separated the first from the second fever phase 60 min after LPS. Subsequently AVP and cortisol plasma levels rose in febrile animals, irrespective of hypothalamic heating and cooling, presumably as a consequence of pyrogenic activation of corticotropin releasing factor (CRF) producing neurons and their reciprocal interaction with TRH neurons on the one hand, and by a reciprocal interaction of the latter with AVP neurons on the other.
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PMID:Hormonal secretion patterns but not autonomic effector responses elicited by hypothalamic heating and cooling are altered in febrile rabbits. 896 49

Glucagon and arginine vasopressin (AVP) enhance renal magnesium conservation through actions within the loop of Henle and the distal tubule. Studies were performed on an immortalized mouse distal convoluted tubule (MDCT) cell line to characterize the cellular actions of these hormones on Mg2+ transport in this segment of the distal tubule. Glucagon and AVP increased cellular cAMP concentrations by about fivefold above basal levels in normal and Mg(2+)-depleted cells. Intracellular free Mg2+ concentration ([Mg2+]i) was determined on single MDCT cells using microfluorescence with mag-fura 2. To assess Mg2+ uptake, MDCT cells were first Mg2+ depleted (0.22 +/- 0.01 mM) by culturing in Mg(2+)-free media for 16 h and then placed in 1.5 mM MgCl2, and the [Mg2+]i was determined. [Mg2+]i returned to basal levels, 0.53 +/- 0.02 mM, with a mean refill rate, d([Mg2+]i/dt, of 164 +/- 5 nM/s. Both glucagon and AVP stimulated Mg2+ uptake into MDCT cells, 196 +/- 11 and 189 +/- 6 nM/s, respectively, at concentrations of 3 x 10(-7) M and 10(-7) M, respectively. Enhanced Mg2+ uptake for each of the hormones was concentration dependent and inhibited by the channel blocker, nifedipine. Hormone stimulation of Mg2+ entry was not dependent on protein synthesis. 8-Bromo-cAMP, 10(-4) M, enhanced Mg2+ uptake (225 +/- 13 nM/s), whereas phorbol esters were without effect. Finally, protein kinase A inhibition prevented glucagon and AVP stimulation of Mg2+ uptake, supporting the notion that the cAMP pathway is important as expected in the hormone action. These studies demonstrate that glucagon and AVP stimulate Mg2+ uptake in MDCT cells and suggest that these hormones act to control magnesium conservation in the convoluted segment of the distal tubule.
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PMID:Glucagon and arginine vasopressin stimulate Mg2+ uptake in mouse distal convoluted tubule cells. 948 27

The distal convoluted tubule reabsorbs significant amounts of filtered magnesium that is under hormonal control. In this study, we describe the effects of aldosterone on Mg2+ uptake in an immortalized mouse distal convoluted tubule (MDCT) cell line. Intracellular free Mg2+ concentration ([Mg2+]i) was determined on single MDCT cells using microfluorescence with mag-fura 2. To determine Mg2+ entry rate into MDCT cells, they were first Mg2+ depleted ([Mg2+]i, 0.22 +/- 0.01 mM) by culturing in Mg(2+)-free media for 16 h and then placed in 1.5 mM MgCl2. The rate of change in [Mg2+]i as measured as a function of time, d([Mg2+]i)/dt, was 164 +/- 5 nM/s in control cells. We have shown that glucagon or arginine vasopressin (AVP) stimulates Mg2+ entry by 63% and 15%, respectively. Incubation of MDCT cells with aldosterone for 16 h did not change the rate of Mg2+ uptake (172 +/- 8 nM/s). However, aldosterone potentiated glucagon- and AVP-stimulated Mg2+ uptake rate up to 330 +/- 39 and 224 +/- 6 nM/s, respectively. Aldosterone also potentiated glucagon- and AVP-induced intracellular cAMP accumulation in a concentration-independent manner. As cAMP stimulates Mg2+ entry in MDCT cells, it is inferred that aldosterone may stimulate Mg2+ uptake through intracellular signaling pathways involving cAMP. The actions of aldosterone were dependent on de novo protein synthesis, as pretreatment of the cells with cycloheximide inhibited aldosterone potentiation of hormone stimulation of Mg2+ uptake and cAMP accumulation. These studies with MDCT cells suggest that aldosterone may modulate the effects of hormones acting within the distal convoluted tubule to control magnesium absorption.
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PMID:Aldosterone potentiates hormone-stimulated Mg2+ uptake in distal convoluted tubule cells. 948 28

An immortalized cell line (designated MDCT) has been extensively used to investigate the cellular mechanisms of electrolyte transport within the mouse distal convoluted tubule. Mouse distal convoluted tubule cells possess many of the functional characteristics of the in vivo distal convoluted tubule. In the present study, we show that MDCT cells also possess a polyvalent cation-sensing mechanism that is responsive to extracellular magnesium and calcium. Southern hybridization of reverse transcribed-polymerase chain reaction (RT-PCR) products, sequence determination and Western analysis indicated that the calcium-sensing receptor (Casr) is expressed in MDCT cells. Using microfluorescence of single MDCT cells to determine cytosolic Ca2+ signaling, it was shown that the polyvalent cation-sensing mechanism is sensitive to extracellular magnesium concentration ([Mg2+]o) and extracellular calcium concentration ([Ca2+]o) in concentration ranges normally observed in the plasma. Moreover, both [Mg2+]o and [Ca2+]o were effective in generating intracellular Ca2+ transients in the presence of large concentrations of [Ca2+]o and [Mg2+]o, respectively. These responses are unlike those observed for the Casr in the parathyroid gland. Finally, activation of the polycation-sensitive mechanism with either [Mg2+]o or [Ca2+]o inhibited parathyroid hormone-, calcitonin-, glucagon- and arginine vasopressin-stimulated cAMP release in MDCT cells. These studies indicate that immortalized MDCT cells possess a polyvalent cation-sensing mechanism and emphasize the important role this mechanism plays in modulating intracellular signals in response to changes in [Mg2+]o as well as in [Ca2+]o.
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PMID:Extracellular Mg2(+)- and Ca2(+)-sensing in mouse distal convoluted tubule cells. 950 2

The distal convoluted tubule plays a significant role in renal magnesium conservation. An immortalized mouse distal convoluted tubule (MDCT) cell line has been extensively used to study the cellular mechanisms of magnesium transport in this nephron segment. MDCT cells possess an extracellular polyvalent cation-sensing mechanism responsive to Mg2+, Ca2+, and neomycin. The present studies determined the effect of Mg2+/Ca2+ sensing on hormone-mediated cAMP formation and Mg2+ uptake in MDCT cells. MDCT cells were Mg2+ depleted by culturing in Mg2+-free media for 16 h, and Mg2+ uptake was measured by microfluorescence after placing the depleted cells in 1.5 mM MgCl2. The mean rate of Mg2+ uptake was 164 +/- 5 nM/s in control MDCT cells. Activation of Mg2+/Ca2+ sensing with neomycin did not affect basal Mg2+ uptake (155 +/- 5 nM/s). We have previously reported that treatment of MDCT cells with either glucagon or arginine vasopressin (AVP) stimulated Mg2+ entry. In the present studies, the addition of extracellular Mg2+ or Ca2+ inhibited glucagon- and AVP-stimulated cAMP formation and Mg2+ uptake in concentration-dependent manner with half-maximal concentrations of approximately 1.5 and 3.0 mM, respectively. Exogenous cAMP or forskolin stimulated Mg2+ uptake in the presence of Mg2+/Ca2+ sensing activation. We infer from these studies that Mg2+/Ca2+-sensing mechanisms located in the distal convoluted tubule may play a role in control of distal magnesium absorption.
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PMID:Mg2+/Ca2+ sensing inhibits hormone-stimulated Mg2+ uptake in mouse distal convoluted tubule cells. 972 7

Receptor antagonists were used to determine which receptor mediates the effect of arginine vasopressin (AVP) and oxytocin (OT) on glucagon release from hamster glucagonoma In-R1-G9 cells. Both AVP (10(-9)-10(-6) M) and OT (10(-8)-10(-5) M) increased glucagon release from In-R1-G9 cells in a concentration-dependent manner and AVP was approximately 30-fold more potent than OT in this aspect. The antagonists with potent V1b receptor blocking activity, CL-4-84 (10(-9)-10(-6) M), dP[Tyr(Me)2]AVP and AO-2-44 (10(-8)-10(-6) M), antagonized the effect of both AVP and OT in a concentration-dependent manner. Other receptor antagonists at 10(-6) M failed to block the effect of AVP and OT; these included a highly selective OT-receptor antagonist, L-366,948 and a V1a/V2 receptor antagonist WK-3-6. However, these antagonists at higher concentrations (10(-5) and 10(-4) M) caused inhibition of AVP- and OT-induced glucagon release. The order of antagonistic potency was estimated as CL-4-84 approximately = dP[Tyr(Me)2]AVP approximately = AO-2-44 > WK 3-6 > L366,948. d[D-3-Pal]VP (10(-8)-10(-5) M), a V1b receptor agonist, also increased glucagon release in a concentration-dependent manner, which was antagonized by dP[Tyr(Me)2]AVP (10(-8)-10(-6) M) and CL-4-84 (10(-9)-10(-6) M), but not by WK-3-6 (10(-6) M) or L-366,948 (10(-6) M). Therefore, the stimulatory effects of both OT and AVP on glucagon release may be mediated by V1b receptors, but not by V1a, V2, or OT receptors.
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PMID:Effects of arginine vasopressin and oxytocin on glucagon release from clonal alpha-cell line In-R1-G9: involvement of V1b receptors. 982 65

1. The aim of the present study was to investigate the transduction pathways elicited by prostaglandin E2 (PGE2) to inhibit hormone-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat nephron. 2. In the OMCD, 0.3 microM PGE2 and low concentrations of Ca2+ ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same process insensitive to Bordetella pertussis toxin (PTX). 3. Sulprostone, an agonist of the EP1/EP3 subtypes of the PGE2 receptor, decreased AVP-dependent cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL. 4. In MTAL, 1 nM sulprostone and PGE2 inhibited by about 90% a same pool of AVP-dependent cyclic AMP content through a PTX-sensitive, Ca2+ -independent pathway. 5. In the OMCD, PGE2 decreased by about 50% glucagon-dependent cyclic AMP synthesis by a process sensitive to PTX and Ca2+ -independent. Sulprostone 1 nM induced the same level of inhibition. 6. These results demonstrate that PGE2 decrease hormone-dependent cyclic AMP accumulation through a G(alpha)i-mediated inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+ concentration in AVP-sensitive cells of the OMCD.
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PMID:Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule. 1019 86

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