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)

A clinical study was conducted whereby the activity of adenyl cyclase in the human platelet was demonstrated. The study showed that this activity can be stimulated and inhibited in vitro. Platelets were isolated from normal donors. The laboratory procedures involved in the study are described in detail. It seems that many of the biologic processes which occur in the human platelet are dependent on the breakdown of ATP (adenosine-tri-phosphate) to, among other substances, AMP (adenosine-3',5' monophosphate). Activity of the adenyl cyclase was stimulated by fluoride, prostaglandin E1, and glucagon; it was inhibited by thrombin, epinephrine, norepinephrine, and serotonin. PG (prostaglandin) E1 at concentrations of 20 ng/ml and above increased adenyl cyclase in 7 experiments by 3-5 times. Even at concentrations as low as 2 ng/ml., PGE2 caused perceptable stimulation. The PGE, while stimulating adenyl cyclase activity, also inhibited aggregation of platelets by a variety of substances. Results of the study suggest that adenosine-3',5' monophosphate may be important in the regulation of platelet adhesiveness.
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PMID:Adenyl cyclase in human platelets: activity and responsiveness. 430 55

In the presence of 3-isobutyl-l-methylxanthine, VIP produced a dose-related (3 X 10(-9)-10(-7) M) increase (8-fold) in cAMP production in isolated HEp-2 cells incubated at 15 degrees C in KRP buffer. Among the peptides structurally related to VIP, including secretin (10(-7) M), pancreatic glucagon (10(-6) M), PHI, somatostatin-14 (10(-6) M), hpGRF (10(-8)-4 X 10(-6) M), GIP (2 X 10(-7) M), only PHI (3 X 10(-7) M and above) is able to activate the cAMP-generating system in HEp-2 cells, but at 10(2) times lower potency. Under the same conditions, histamine (10(-3) M) was also ineffective, while PGE2 (10(-7)-10(-4) M) increased (4-fold) basal cAMP levels in HEp-2 cells. The VIP effect is related to the interaction of the peptide on VIP recognition sites (125I-VIP-binding capacity), coupled to the membrane-bound adenylate cyclase. The results indicate that the transformed laryngeal cell line HEp-2 possesses a receptor-cAMP system preferentially activated by VIP (relative potencies: VIP greater than PHI much greater than other peptides of the secretin family), and suggest that this neuropeptide could modulate biological functions in normal laryngeal epithelia in man.
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PMID:Activation of the cAMP-generating system by vasoactive intestinal polypeptide (VIP) in the human laryngeal malignant cell line HEp-2. 608 15

The effects of PGE1, PGE2 and PGD2 on somatostatin, insulin and glucagon secretions were investigated at various glucose concentrations using the isolated perfused rat pancreas. At glucose concentrations varying from 0 to 16.7 mM, PGE1 and PGE2 enhanced somatostatin release in a glucose dose-dependent manner. PGE1 did not significantly stimulate insulin secretion at glucose concentrations of 4.4 mM or less, but did at glucose concentrations of 8.8 mM or more, PGE2 augmented insulin release at 4.4 and 16.7 mM glucose, but not in the absence of glucose. Glucagon release was induced by PGE1 and PGE2 in a biphasic pattern with the maximal response in the absence of glucose. Like PGE1 and PGE2, PGD2 stimulated insulin and glucagon release in a glucose-related fashion. PGD2, however, was not capable of stimulating somatostatin release at various glucose concentrations even in the presence of 16.7 mM glucose. In conclusion, PGE1, PGE2, and PGD2 increase insulin and glucagon secretion in a glucose-dependent manner. PGE1 and PGE2 also stimulate somatostatin release, but PGD2 has no effect on somatostatin secretion at the doses studied.
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PMID:Different effects of prostaglandin E1, E2 and D2 on pancreatic somatostatin release. 615 34

Prostaglandin E (PGE) has several effects on glucose homoeostasis and insulin secretion. The same events can be induced by alpha-adrenergic stimulation, which is known to stimulate PGE synthesis. To evaluate the hypothesis that PGE may be one intracellular mediator for certain alpha-adrenergic events, we examined the effects of a known PG synthesis inhibitor Sodium salicylate (SS) (40 mg/min iv) on the alpha-adrenergic effects of epinephrine (Epi) at two doses (3 and 6 micrograms/min) in normal male subjects. The lower dose of epinephrine diminished the acute insulin response (AIR) after a 20-g intravenous glucose pulse (control, 463 +/- 149; epinephrine, 97 +/- 38% of basal insulin, mean +/- SE, n = 6, P < 0.02); SS markedly augmented the AIR during epinephrine towards control values (339 +/- 137%; P < 0.02). In 12 subjects, the higher dose of Epi abolished the AIR. When similar studies were performed during a SS infusion, the AIR was partially restored (96 /+- 27% of basal insulin, n = 12, P < 0.01). Similarly, partial reversal of this alpha-adrenergic effect of Epi was observed with indomethacin, another inhibitor of PG synthesis. At both doses of Epi, SS augmented the glucose disappearance rate (KG) after the glucose pulse (P < 0.001). Sodium salicylate also increased basal glucagon levels (P < 0.05). In contrast, SS did not affect the glycemic response, the suppression of basal insulin levels, or the hemodynamic responses induced by adrenergic stimulation. We conclude that two prostaglandin synthesis inhibitors partially reverse the alpha-adrenergic inhibition of the AIR to glucose caused by Epi, without affecting other adrenergic events. The data are compatible with a role for prostaglandins in alpha-adrenergic events selectively in the pancreatic islet.
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PMID:Prostaglandin synthesis inhibitors reverse alpha-adrenergic inhibition of acute insulin response to glucose. 625 5

In view of reports that prostaglandins influence insulin and glucagon secretion, we have studied PGE2, insulin and glucagon release from fragments (15-20 mg) of human insulinoma tissue incubated in vitro in the absence or presence of indomethacin (100 mumol/liter) an inhibitor of prostaglandin synthesis. Acid-ethanol extraction of this tissue showed the following hormonal contents : insulin : 7.17 U and glucagon 84.4 ng per g of tissue (wet weight). In the absence of indomethacin, the mean release of PGE2, insulin and glucagon into the incubation medium was 3.65 +/- 1.3 pmol, 10.5 +/- 1.2 mU and 708.4 +/- 141.8 pg in two hours (mean of 5 vials containing 2 fragments of 15-20 mg of tissue). PGE2 release was significantly inhibited in the presence of indomethacin (0.89 +/- 0.23 pmol). This effect was associated with a significantly higher insulin (16.8 +/- 1.9 mU/2 hours) and lower glucagon (176 +/- 19.7 pg/2 hours) release. These results support the view that insular tissue possesses a prostaglandin synthesis system which positively modulates glucagon secretion whereas it negatively influences insulin release.
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PMID:Insulin, prostaglandin E2 and glucagon release by human tissue incubated in vitro. Influence of indomethacin. 626 25

Prostaglandin E (PGE) receptor density in hepatic plasma membranes can be down-regulated by in vivo exposure to the 16,16-dimethyl analog of PGE2, and this is associated with desensitization of PGE-sensitive adenylate cyclase. These studies examined adenylate cyclase response to other agonists in membranes whose PGE receptor density was 51% decreased and whose maximal PGE-stimulated adenylate cyclase activity was 31% decreased. Down-regulated membranes had a 37% decrease in their maximal response to glucagon, indicating that treatment with the PGE analog had induced both homologous and heterologous desensitization. To determine whether adenylate cyclase had been affected, stimulation with NaF, guanyl 5'-yl imidodiphosphate (GppNHp), and forskolin was examined in both intact and solubilized membranes. Intact membranes had decreased adenylate cyclase responses to all three stimulators (NaF, -41%; GppNHp, -25%; forskolin, -41%) as did solubilized membranes (NaF, -51%; GppNHp, -50%; forskolin, -50%), suggesting alterations in adenylate cyclase rather than indirect membrane effects. Cholera toxin activation and labeling were examined to more directly assess whether the guanine nucleotide (G/F) regulatory component of adenylate cyclase had been affected. Cholera toxin activation was 42% less in down-regulated membranes, and these membranes incorporated less label when the incubation was performed in the presence of [32]NAD. Solubilized G/F subunit activity from down-regulated membranes was less effective in reconstitution of adenylate cyclase activity from cyc- cell membranes than G/F activity from control membranes. These data indicate that in vivo exposure to the PGE analog causes both homologous and heterologous desensitization of adenylate cyclase as well as an apparent quantitative decrease in G/F.
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PMID:Prostaglandin E-induced heterologous desensitization of hepatic adenylate cyclase. Consequences on the guanyl nucleotide regulatory complex. 630 97

The effect of glucagon and its interaction with histamine on adenylate cyclase (AC), cellular cAMP and [14C]aminopyrine ( [14C]AP) uptake, a reliable index of parietal cell H+ production, was studied in isolated rat gastric cells. AC activation in response to glucagon and histamine correlated with the number of parietal cells. Glucagon (10(-10)-10(-6) mol/l) increasingly stimulated AC (maximal effect: 92% by 10(-7) mol/l) and cellular cAMP (86% by 10(-9) mol/l) of fractions enriched with 80% parietal cells but did not cause a pronounced change of the histamine-stimulated enzyme. If there was any interaction, the effect of both hormones was additive. Glucagon neither changed basal [14C]AP uptake nor interfered with that in response to histamine. The data suggest that if glucagon activates a parietal cell AC this process is not followed by parietal cell H+ production. Furthermore, unlike other inhibitors such as somatostatin or PGE2, glucagon does not reduce acid secretion via the cAMP system of the parietal cell.
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PMID:Adenylate cyclase and H+ production of isolated rat parietal cells in response to glucagon and histamine. 632 13

The influence of different levels of inhibition of prostaglandin (PG) synthesis on the release of insulin and glucagon was investigated in the basal state (5.6 mM glucose) and in response to 30-min perfusion of 16.7 mM glucose using the isolated perfused rat pancreas model. Flurbiprofen (FLR), a potent and selective inhibitor of PG synthesis, was present in the perfusate during the entire experimental period at a concentration of 10(-8), 5 X 10(-8), or 10(-6) M; control experiments were performed without the drug. Levels of immunoreactive PGE2, PGF2 alpha, insulin, and glucagon were measured in the portal venous effluent. FLR inhibited PG synthesis in a dose-related manner; PGE2 was inhibited more than PGF2 alpha. Basal and glucose-induced secretion of insulin was augmented by FLR at 5 X 10(-8) M, but was inhibited at 10(-6) M. At 10(-6) M FLR, basal glucagon secretion was inhibited; glucose-induced suppression still occurred without any potentiation. We conclude that 1) endogenous PGs modulate the secretion of insulin and glucagon; 2) divergence of the effects of low and high levels of inhibition of PG biosynthesis on insulin release may be due to altered tissue proportions of various PGs and related autacoids; and 3) the predominant effect of endogenous PGs on glucagon release is tonic stimulation.
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PMID:The effect of flurbiprofen, a potent inhibitor of prostaglandin synthesis, on insulin and glucagon release from isolated rat pancreas. 636 3

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

Enhancement of arachidonic acid metabolism results in increased insulin secretion. To determine which pathways of arachidonic acid metabolism were involved in this stimulation, we studied the effects of various inhibitors of arachidonate metabolism on arginine-induced insulin and glucagon secretion in the isolated, perfused rat pancreas. The release of PGE2 from the pancreas was monitored to document the efficacy of the inhibitory drugs. p-Bromophenacyl bromide, a phospholipase A2 inhibitor, diminished PGE2 release and significantly inhibited both the early and late phases of insulin and glucagon release in response to arginine. Flurbiprofen, a specific cyclooxygenase inhibitor, decreased the early phase of insulin release and inhibited both phases of arginine-stimulated glucagon secretion; these decreases were concurrent with a large inhibition of PGE2 release. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, at a dose of 10(-5) M did not affect PGE2 release, inhibited the early phase of insulin release, and did not modify glucagon secretion. The combination of flurbiprofen and nordihydroguaiaretic acid, although the most potent in inhibiting PGE2, lowered only the early phase of insulin and had no effect on glucagon secretion. We conclude that: (1) endogenous cyclooxygenase-derived metabolites of arachidonic acid promote insulin and glucagon release, (2) endogenous lipoxygenase products preferentially stimulate insulin release, and (3) phospholipase A2 activity has an intrinsic modulatory effect on insulin and glucagon secretion.
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PMID:Possible role of endogenous arachidonic acid metabolites in stimulated release of insulin and glucagon from the isolated, perfused rat pancreas. 643 60


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