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 uptake of macromolecular markers by fluid pinocytosis in the rat yolk sac was inhibited by glucagon, with half-maximal effect at a hormone concentration of approximately 3 X 10(-8) M. Glucagon had no effect on the cellular distribution of the marker subsequent to its uptake. Rates of uptake promptly returned to normal when the yolk sacs were transferred from a glucagon-containing to a glucagon-free medium. Epinephrine also inhibited, but only at much higher concentrations. The effect of the latter was augmented by theophylline. Insulin (10(-6) M) had no effect when added alone or with an inhibitory level of glucagon (10(-7) M). The presumption that the hormone effect was mediated by cyclic AMP was supported by the findings that the cellular levels of cyclic AMP were elevated in the presence of glucagon and that dibutyryl cyclic AMP could replace glucagon as an effective inhibitor. The conclusion that the hormone effect was on uptake rather than on subsequent regurgitation was based on the linearity of accumulation in both the presence and absence of glucagon and the inability of glucagon to stimulate loss of invertase from preloaded cells. Colchicine and vinblastine also inhibited uptake. This finding and those of others which are discussed suggest the possibility that effects of cyclic nucleotides on certain cell functions may involve their regulation of microtubular status.
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PMID:Effect of glucagon on pinocytosis by the yolk sac of the rat. 90 54

The aim of this study was to localize cells immunoreactive for glutamate decarboxylase (GAD), the enzyme of GABA synthesis, in pyloric and oxyntic regions of the rat stomach as well as in the rat and mouse pancreas. GAD immunocytochemistry was carried out on polyethylene glycol or cryostat sections of alkaline paraformaldehyde fixed tissue, with simultaneous immunolabelling of various gastro-pancreatic hormones for topographical comparison. In the rat stomach, nerve fibers displaying intense GAD-like immunoreactivity were seen in the myenteric plexus, the circular muscular layer, the submucosa and the lamina propria of the mucosa. But, they were absent from the submucous plexus. Colchicine treatment of the rats allowed to detect some labelled perikarya in the myenteric plexus suggesting that the GABAergic innervation is at least partly intrinsic to the stomach. In the oxyntic and pyloric mucosa, endocrine cells appeared immunostained for GAD. However, the nature of their hormones remained unknown since double immunodetections revealed that they were immunoreactive neither for gastrin nor for somatostatin. In the rat and mouse pancreas, GAD-like immunoreactivity was found in islet cells which corresponded only to insulin-secreting cells. Somatostatin-, glucagon- and pancreatic polypeptide-immunopositive cells were devoid of GAD immunolabelling. No GAD-like immunoreactivity was detected in the exocrine tissue and innervation. These results strenghten the hypothesis that GABA is not only a neurotransmitter in the stomach but that it could also be an endocrine or paracrine factor in the stomach and pancreas.
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PMID:Localization of GAD-like immunoreactivity in the pancreas and stomach of the rat and mouse. 178 8

The present studies were carried out to clarify the mechanism of glucagon choleresis in guinea pigs. At the infusion rate of 1.4 nmol.min-1.kg-1, glucagon increased bile flow from 206.6 +/- 14.3 to 302.6 +/- 35.0 microliters.min-1.kg-1 and bicarbonate biliary concentration from 63.7 +/- 4.2 to 75.5 +/- 5.9 meq/l. Measurements of bile acid excretion in bile, the biliary tree volume, and of the hormone choleretic effect in guinea pigs with proliferated bile ductules/ducts induced by alpha-naphthylisothiocyanate feeding indicated that glucagon, unlike secretin, stimulated canalicular bile flow. Inhibition of prostaglandin synthesis by indomethacin administration (5 mg.kg-1.h-1) did not modify the choleretic effect of glucagon, and infusion of a glucagon analogue (TH-glucagon, 1.4 nmol.min-1.kg-1), which did not increase hepatic formation of adenosine 3'5'-cyclic monophosphate (cAMP), failed to stimulate bile flow. Like the parent hormone, however, TH-glucagon augmented plasma glucose levels and stimulated formation of inositol phosphates. Colchicine pretreatment (0.5 mg/kg ip) almost entirely prevented the choleretic effect of glucagon but did not modify spontaneous and bile acid-induced bile flow and the stimulatory effect of the hormone on glucose release and on hepatic formation of cAMP and inositol phosphates. Finally, glucagon produced a large increase in the biliary entry of horseradish peroxidase, even though this effect was transient and was not coupled to the increase in bile flow. These results indicate that glucagon choleresis in the guinea pig is not secondary to prostaglandin release, is canalicular in origin, involves bicarbonate secretion, is mediated by cAMP, and requires an intact microtubular system.
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PMID:mechanism of glucagon choleresis in guinea pigs. 217 15

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.
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PMID:Alcoholic liver disease. 222 93

Postprandial elevation of 5-phosphoribosyl 1-diphosphate (PPRibP) concentration in the mouse liver (Lalanne, M. and Henderson, J.F. (1975) Can. J. Biochem. 53,394-399) was further studied regarding the effects of protein intake and the underlying mechanisms. The extent and duration of the increase depended on the quantity and quality of proteins ingested. The order of effectiveness of various diets was as follows: 60% casein greater than 20% egg albumin greater than 20% casein greater than 20% gelatin = 20% gluten greater than 20% zein greater than 0% casein. Hepatic purine and pyrimidine biosyntheses de novo, as measured by labelled tracer incorporation, increased with increasing protein intake. Nicotinic acid incorporation into NAD increased equally, whether casein-containing or casein-free diets were given. Therefore, the increase of PPRibP level may be brought about by increase in its synthesis. Administration of glucagon or epinephrine similarly elevated the hepatic level of PPRibP. Somatostatin, known to inhibit secretion of pancreatic hormones, suppressed the casein-diet-dependent PPRibP level increase. Colchicine markedly inhibited the casein-diet- and glucagon-dependent responses, but not the epinephrine effect. It is likely that glucagon is a major factor in mediation of the protein-diet-dependent PPRibP level increase and that the cytoskeleton is involved in the glucagon-mediated response.
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PMID:Protein-diet-induced elevation of 5-phosphoribosyl 1-diphosphate concentrations in mouse liver associated with increased syntheses of various nucleotides and the possible involvement of glucagon. 620 43

The effects of the microtubule inhibitor, colchicine, on insulin or glucagon stimulation of alpha-amino[1-14C]-isobutyric acid (AIB) transport were investigated in isolated hepatocytes from normal fed rats. Under all conditions tested, AIB uptake appeared to occur through two components of transport: a low affinity (Km approximately 50 mM) component and a high affinity (Km approximately 1 mM) component. Within 2 h of incubation, insulin and glucagon, at maximal concentrations, increase AIB (0.1 mM) uptake by 2- to 3-fold and 4- to 6-fold, respectively. Colchicine, at the low concentration of 5 X 10(-7) M, slightly reduces basal AIB transport, decreases by 80% the simulatory effect of insulin, and diminishes by 40% the stimulatory effect of either glucagon or dibutyryl cAMP. Kinetic analysis of AIB influx indicates that the drug inhibits the increase in Vmax of a high affinity (Km approximately 1 mM) component of transport stimulated by insulin or glucagon, without affecting the kinetic parameters of a low affinity component of transport (Km approximately 50 mM). Various short term hormonal effects of insulin and glucagon (changes in glucose, urea, and lactate production) were found not to be modified by the drug. Vinblastine elicits similar changes as colchicine on AIB uptake. Lumicolchicine, a colchicine analogue that does not bind to tubulin, has no effect. The concentration of colchicine (10(-7) M) required for half-maximal inhibition of hormone-stimulated AIB transport is in the appropriate range for specific microtubule disruption. These data suggest that microtubules are involved in the regulation of the insulin or glucagon stimulation of AIB transport in isolated rat hepatocytes.
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PMID:Role of microtubules in insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes. 626 Jul 94

Glucose stimulation of [32P]-prelabelled pancreatic islets induced an increased incorporation of radioactivity into phosphatidylinositol. Glucagon and agents that increases cAMP in the islet did not affect phosphatidylinositol turnover, in spite of increased release of insulin. Furthermore, the potent inhibitor of insulin release, somatostatin did not alter phospholipid metabolism. Colchicine inhibited glucose-stimulated turnover of phosphatidylinositol as well as insulin release. These results may suggest that: (1) cAMP and phosphatidylinositol turnover are involved in different transmembrane control system for regulating insulin release; and (2) the function of microtubules modulate phospholipid metabolism.
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PMID:Effects of insulin secretagogues and inhibitors on phospholipid metabolism in Langerhans' islets of rat pancreas. 630 18

Lipoprotein production by freshly isolated rat hepatocytes in suspension was studied during short (1--3 hr) incubation periods. The hepatocytes release very low density (d < 1.01 g/ml) lipoprotein (VLDL) particles, which as a group a) contain triaclyglycerols, phospholipids, free cholesterol, and cholesteryl esters in molar proportions of 100:21:8:4; b) have a mean diameter 1.5-fold larger than those of plasma VLDL; c) have a similar electrophoretic mobility as plasma VLDL; and d) carry apoproteins B and E as major, and apoproteins AI and C as minor, protein components. These apoproteins in the secreted VLDL can be newly synthesized during the incubation, as indicated by the incorporation of [14C]leucine. The secretion of VLDL by the hepatocytes is inhibited by addition of glucagon or dibutyryl cyclic AMP, and stimulated by added palmitate; thus, as in the whole liver, the secretory process is under hormonal or substrate control also in the isolated cells condition. Phospholipids and free cholesterol are also released as components of particles with higher densities, ranging from 1.03--1.08 g/ml, and from 1.10 to 1.24 g/ml. Colchicine and cycloheximide, while strongly suppressing VLDL secretion, inhibit the release of these other particles to a lesser extent (d 1.03--1.08 g/ml) or not at all (d > 1.10 g/ml). These particles with higher densities have not been positively identified; the latter group is dissimilar to the high density lipoprotein, which occurs in rat liver perfusates, or to rat bile micelles.
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PMID:Lipoprotein secretion by isolated rat hepatocytes: characterization of the lipid-carrying particles and modulation of their release. 741 81

To elucidate mechanisms of glucagon-induced bicarbonate-rich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pHi) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pHi, significantly stimulates the Cl-/HCO3- exchange activity. The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3- exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3- exchange was individually blocked by two specific and selective inhibitors of protein kinase A, Rp-cAMPs (10 microM) and H-89 (30 microM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl- channel blocker, NPPB (10 microM), showed no effect on either the basal or the glucagon-stimulated Cl-/HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 microM), completely blocked the glucagon stimulation of the Cl-/HCO3- exchange; however, this effect was achieved through a significant inhibition of the glucagon-stimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3- exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pHi or at acid pHi values. In contrast, glucagon, at basal pHi, stimulated the Na(+)-HCO3- symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3- exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis.
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PMID:Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets. 763 59

As glucagon is known to cause a receptor-mediated increase in intracellular calcium and cyclic AMP, we have developed a novel method of evaluating the integrity of the signal transduction and transport system using glucagon-induced changes in indocyanine green (ICG) excretion. The kinetics of the hepatocellular concentration of ICG at 4-second intervals was analyzed by near-infrared spectroscopy in vivo on the liver surface. After intravenous injection of 0.5 mg/kg ICG to rabbits, absorbance of ICG increased and then decreased according to the two-compartment model: ICG(t) = -Aexp(-alphat) + Bexp(-betat), where alpha and beta (min(-1)) indicate the time constants of uptake and excretion, respectively. During the excretion phase, 40 microg/kg glucagon was infused as a bolus via the portal vein. A biphasic acceleration and retardation of ICG excretion from the baseline exponential decay was observed in the controls. In order to perturb the glucagon response, colchicine, ouabain, wortmannin and an ischemia-reperfusion insult were employed. Colchicine, ouabain and wortmannin abolished the biphasic acceleration and retardation of ICG excretion. Glucagon response was absent upon the ischemia-reperfusion insult. The observed biphasic response to glucagon clearly indicates that glucagon modulates bile canalicular contraction and peristalsis via the two glucagon receptors and these second messengers. The glucagon response requires the integrity of signal transduction, cytoskeleton structure, myosin function, and bile canalicular pump.
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PMID:Receptor-mediated biphasic alteration of hepatocellular transport from hepatocyte to bile canaliculi as measured by near-infrared spectroscopy: a novel test with glucagon for biliary excretion. 1459 29


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