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)

The In-R1-G9 cell line is one of the clones derived from the In-111-R1 hamster insulinoma cell line and produces glucagon. The secretory responses of In-R1-G9 cells were further examined to characterize the nature of the cells. Vincristine had no effect on glucagon secretion and colchicine enhanced glucagon secretion slightly after a short incubation. Two calmodulin inhibitors, trifluoperazine and chlorpromazine, did not affect glucagon secretion. Monensin at 10(-8) M suppressed glucagon secretion by 50%. Secretion of glucagon was calcium-dependent. The addition of A23187 to the incubation medium resulted in a 180% increase over control for 1 h and calcium deprivation from the medium suppressed glucagon secretion markedly. Theophylline, a phosphodiesterase inhibitor, caused a 230% increase in glucagon secretion. An experiment using cycloheximide suggested that newly synthesized glucagon appears in the medium at 30 min. This cell line should be useful for various experiments in many fields of research.
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PMID:Characterization of secretory responses of a glucagon-producing In-R1-G9 cell line. 283 60

The infusion of a solution containing triiodothyronine, amino acids, glucagon, and heparin (TAGH solution) triggered rat liver cell proliferation. It also induced a transient prereplicative surge of cytosolic calmodulin (between 6 and 20 hr postinfusion) similar to that observed in liver cells proliferatively activated by partial hepatectomy. The injection of the beta-adrenergic blocker dl-propanolol (20 mg/kg of body weight) at the time of the infusion prevented this transient rise of cytosolic calmodulin and also inhibited the early prereplicative surge of total liver cyclic AMP, which usually occurred between 1 and 4 hr after infusion. Propanolol also inhibited the early prereplicative surge of cyclic AMP and the increase of calmodulin in liver cells proliferatively activated by partial hepatectomy. The infusion of a solution containing cyclic AMP (5 mumoles) and theophylline (10 mg) into normal rats produced an increase of cytosolic calmodulin similar to that observed after infusion of TAGH solution or after partial hepatectomy. Thus it seems that the prereplicative rise of cytosolic calmodulin observed in proliferatively activated liver cells may be regulated by the early prereplicative surge of cyclic AMP.
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PMID:Possible cyclic AMP-dependence of the prereplicative surge of cytosolic calmodulin in proliferatively activated rat liver cells. 283 43

The intravenous administration of glucagon to anesthetized rats resulted within 5 min in a 20% drop in the hepatic phosphorylase phosphatase activity, as measured in a post-mitochondrial supernatant at low dilution, but it did not affect the activity of glycogensynthase phosphatase. On the other hand, the injection of insulin plus glucose caused increases by about 35% in both phosphatase activities. Upon subcellular fractionation these effects were recovered in the cytosol, but not in the glycogen/microsomal fraction. However, activity changes in the latter fraction were observed after recombination with the liver cytosol from a hormone-treated animal. Preincubation of the liver cytosol with modulator protein (a specific inhibitor of type-1 protein phosphatases) cancelled the activity changes induced by insulin plus glucose. No hormonal effects on hepatic protein phosphatase activities were observed when the fractions were either diluted an additional 10-fold or pretreated with trypsin. An acute hormonal regulation of protein phosphatases could also be demonstrated in the perfused liver. When added to the perfusion medium, glucose as well as insulin increased the cytosolic protein phosphatase activities by about 25%. Their effect was additive, irrespective of the order of addition. On the other hand, the addition of glucagon and/or vasopressin resulted in a 20% drop in the phosphorylase phosphatase activity. The presence of glucagon did not interfere with the effectiveness of insulin, and vice versa. The changes in the phosphorylase phosphatase activities induced by glucagon, insulin, and glucose represented changes in the Vmax only. We propose that the acute control of the hepatic glycogen synthase phosphatase and phosphorylase phosphatase activities is mediated by transferable, cytosolic effector(s).
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PMID:Acute regulation of hepatic protein phosphatases by glucagon, insulin, and glucose. 284 53

Vasopressin (AVP) plays a key role in maximal urine concentration by stimulating NaCl reabsorption in the medullary thick ascending limbs of Henle (MTAL) and by increasing water permeability in the medullary collecting tubules (MCT). These effects of AVP in MTAL and MCT are mediated by activation of adenylate cyclase. Because effects of high ambient Ca2+ on AVP-sensitive adenosine 3',5'-cyclic monophosphate (cAMP) production are quite different in MTAL and MCT, we examined whether the Ca2+-calmodulin system is involved differently in AVP-sensitive cAMP production in MTAL and MCT of mouse kidney using two dissimilar calmodulin inhibitors, trifluoperazine (TFP) and W-7. TFP and W-7 inhibited AVP-sensitive cAMP production in both nephron segments in a dose-dependent manner with maximal inhibition of both agents being greater than 90%. A half-maximal inhibition by TFP and W-7 was about 45, 100 microM in MTAL and about 40, 40 microM in MCT, respectively. The inhibitory effect of W-5, a chemically similar to W-7 but less potent calmodulin inhibitor, was significantly less than that of W-7 in both nephron segments. TFP and W-7 but not W-5 also inhibited glucagon-sensitive cAMP production in MTAL. W-7 inhibited forskolin-sensitive cAMP production but the inhibition by W-5 was significantly less than that by W-7 in MTAL and MCT. Results suggest that AVP-sensitive cAMP production is MCT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AVP-sensitive cAMP production is dependent on calmodulin in both MTAL and MCT. 284 48

Agents such as 5'-guanylyl-imidodiphosphate(GppNHp), fluoride and forskolin did not activate adenylate cyclase from Tetrahymena. In addition, the cyclase was not stimulated by hormones including catecholamines and glucagon when assayed with or without GppNHp at conditions where they increased adenylate cyclase activity from rat heart. Sodium azide, NaNO2 or N-methyl-N'-nitro-N-nitroguanidine (MNNG) failed to activate Tetrahymena guanylate cyclase. Adenylate cyclase activity was activated at low free Ca2+ level and inhibited at high levels, while guanylate cyclase activity was activated by Tetrahymena calmodulin only at high physiological concn of Ca2+.
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PMID:Regulation by calcium of hormone-insensitive adenylate cyclase and calmodulin-dependent guanylate cyclase in Tetrahymena plasma membrane. 285 63

ATP-citrate lyase and acetyl-CoA carboxylase purified from lactating rat mammary gland are phosphorylated stoichiometrically by the calmodulin-dependent multiprotein kinase from rabbit skeletal muscle. The reactions are completely dependent on the presence of both Ca2+ and calmodulin. ATP-citrate lyase and acetyl-CoA carboxylase are also phosphorylated stoichiometrically by the Ca2+- and phospholipid-dependent protein kinase (protein kinase C) purified from bovine brain. Phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ and phosphatidylserine. The calmodulin-dependent and phospholipid-dependent protein kinases phosphorylate the same serine residue on ATP-citrate lyase that is phosphorylated by cyclic-AMP-dependent protein kinase. The sequence of the tryptic peptide containing this site on the mammary enzyme is identical with the sequence of the peptide containing the site on ATP-citrate lyase that is phosphorylated in isolated hepatocytes in response to insulin and/or glucagon. The calmodulin-dependent, phospholipid-dependent and cyclic-AMP-dependent protein kinases phosphorylate distinct sites on acetyl-CoA carboxylase. However, one of the three phosphorylated tryptic peptides derived from enzyme treated with the phospholipid-dependent kinase is identical with the major phosphopeptide (T1) derived from enzyme treated with cyclic-AMP-dependent protein kinase. Phosphorylation of acetyl-CoA carboxylase by the phospholipid-dependent protein kinase inactivates acetyl-CoA carboxylase in a similar manner to cyclic-AMP-dependent protein kinase. With either protein kinase slightly greater phosphorylation and inactivation is seen after pretreatment of acetyl-CoA carboxylase with protein phosphatase-2A, but the effects of the protein phosphatase treatment are not completely reversed. Inactivation by the phospholipid-dependent protein kinase is Ca2+- and phospholipid-dependent, is reversed by protein phosphatase-2A, and correlates with the degree of phosphorylation. The relevance of these findings to insulin- and growth-factor-promoted phosphorylation of ATP-citrate lyase and acetyl-CoA carboxylase in intact cells is discussed.
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PMID:Characterization of the phosphorylation of rat mammary ATP-citrate lyase and acetyl-CoA carboxylase by Ca2+ and calmodulin-dependent multiprotein kinase and Ca2+ and phospholipid-dependent protein kinase. 287 35

Glucose is the main stimulator and physiological regulator of insulin secretion. The great sensitivity of the B cell to glucose variations between 1 g/l (5.5 mM) and 3 g/l (16.6 mM) and its rapid response ensure the constant adaptation of its secretion to plasma glucose level. The cellular mechanisms involved in insulin response can be schematically represented in three stages: The first stage is the recognition of the insulinotropic agent. In the case of glucose, this involves its metabolism. The second one is the coupling of the recognition process to activation of the effector system and implies a series of intracellular signals. Coupling factors include metabolites and cofactors, ions, cyclic AMP, polyphosphoinositides. The result of all these cellular events is the increase in cytosolic Ca2+ and the activation of protein-kinases: Ca2+-calmodulin-, cAMP- and Ca2+-phospholipid-dependent protein kinases. The last stage corresponds to a mechanical one, involving granule migration and extrusion. The polymerization of microtubules associated with contraction of microfilaments would cause granule movement. Ca2+-calmodulin-dependent protein kinases would play a major role. While glucose is the main stimulator of insulin secretion, numerous factors can influence it. The regulation of this secretion is essentially under the control of three classes of elements: nutrients, hormones and neurotransmitters. As to stimulation of insulin secretion by nutrients, it seems to be secondary to an increase in intracellular metabolism. However it must be underlined that the insulin secretory effect of most nutrients requires the presence of glucose which is consequently a permissive factor. A number of gastrointestinal and pancreatic hormones stimulate, in presence of glucose, insulin secretion and play an essential role during food intake, which results in a better fitting of insulin secretion to energy supply. The term "incretin" designates a hormonal transmitter between the gastrointestinal tract and the B cell; the "incretin" factors are included in what is termed enteroinsular axis. Of the gastrointestinal hormones, GIP (gastric inhibitory polypeptide) appears to play the most important physiological role in potentiating the insulin secretory effect of glucose. Pancreatic glucagon potentiates the effect of glucose too; it is difficult to distinguish between its endocrine and paracrine role. The pancreatic B cell is under neural regulation. The cholinergic system stimulates insulin secretion and the B cell is fitted with receptors of muscarinic type.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Current data on insulin secretion and its regulation]. 288 Oct 28

The effects of certain peptides of the glucagon family on calmodulin activity were determined from their capacity to inhibit a calmodulin-dependent form of phosphodiesterase. Vasoactive intestinal peptide and secretin were potent inhibitors of calmodulin activity, having IC50 values of 0.5 microM and 2 microM, respectively. By contrast, glucagon failed to inhibit calmodulin activity even at concentrations of 100 microM. None of these compounds significantly inhibited the basal activity of phosphodiesterase at concentrations up to 100 microM. These findings support the suggestion that important structural features of peptides for anticalmodulin activity include a net positive charge and a hydrophobic surface.
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PMID:Inhibition of calmodulin-stimulated phosphodiesterase activity by vasoactive intestinal peptide. 298 33

Preliminary studies (Lineweaver-Burk, Ca2+ calmodulin sensitivity) suggest that oral mucosa contains at least two cyclic AMP phosphodiesterases, one a high affinity (low Km) enzyme and the other a low affinity (high Km) enzyme. Analysis of the distribution of both enzymatic forms during oral mucosal regeneration revealed that the low Km, and high Km cAMP phosphodiesterase activities were significantly elevated prior to the first wave of cAMP accumulation and during the second cAMP wave. Although the cAMP peaks declined between 20-24 h, both cAMP phosphodiesterases remained significantly elevated at the wound site. The apparent Km of the low Km form increased from 5.3 to 7.5 microM, while that of the high Km form remained essentially unaltered 20 h after wounding. The low Km, and high Km cAMP phosphodiesterase activities in normal rat oral mucosa were not affected by epinephrine or insulin; were slightly inhibited by glucagon, and significantly inhibited by methylprednisolone. Imidazole and histamine activated both forms and theophylline was inhibitory to the enzyme. The high Km cAMP phosphodiesterase was sensitive, and the low Km form insensitive to Ca2+ calmodulin stimulation.
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PMID:Changes in cAMP phosphodiesterase activity during oral mucosal regeneration. 300 61

In this study a synthetic analog of the calmodulin-binding domain of myosin light chain kinase, a 17-amino-acid peptide (M5) was used to examine the possible role of calmodulin in melanotropin receptor function. Binding of beta-melanocyte-stimulating hormone to its membrane receptor and subsequent stimulation of adenylate cyclase (AC) were found to be specifically inhibited by M5 in a dose-dependent and noncompetitive manner, both in intact M2R melanoma cells and in a plasma membrane preparation derived thereof. Half-maximal inhibition of both hormone binding and melanotropin-sensitive AC activity was shown to occur at approximately 1 microM M5. In contrast, stimulation of AC by prostaglandin E1, guanosine 5'-O-(3-thio)triphosphate, forskolin, and unstimulated enzyme activity were unaffected by the presence of M5, under the same assay conditions. Furthermore, addition of a molar excess of calmodulin to the AC assay completely abolished the inhibitory effects of the peptide on melanotropin-stimulated AC activity. Other peptides of similar size, which bind to calmodulin with low affinity (e.g. glucagon, somatostatin, and vasoactive intestinal peptide), were shown to be totally ineffective in inhibiting melanotropin-sensitive AC. These findings, along with those shown previously for other antagonists of calmodulin, suggest a role for an M5-binding protein, as of yet unidentified, involved in the regulation of the melanotropin receptor function.
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PMID:A synthetic analog of the calmodulin-binding domain of myosin light chain kinase inhibits melanotropin receptor function and activation of adenylate cyclase. 336 68


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