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)

Hepatocytes and Kupffer cells were separated from rat liver after prelabeling the Kupffer cells with colloidal iron and perfusion of the liver with digestive enzymes. The activity of several enzymes from Kupffer cells and hepatocytes was compared to validate this method of cell separation. The ratios of hepatocyte to Kupffer cell specific activities of glucose-6-phosphatase, 5'-nucleotidase, adenylate cyclase, and acid phosphatase were 20, 0.39, 0.18, and 0.078, respectively. Adenylate cyclases from hepatocytes and Kupffer cells were stimulated by fluoride ion, GTP, and catecholamines. Hepatocyte adenylate cyclase was also stimulated by glucagon, secretin, vasoactive intestinal polypeptide, and by prostaglandin E1, whereas, the Kupffer cell enzyme was completely insensitive to these hormones. The stimulation of hepatocyte adenylate cyclase by combinations of glucagon plus secretin, or glucagon plus vasoactive intestinal polypeptide, were equivalent to the sum of the individual stimulations. This suggests that the hepatocyte has specific receptors for glucagon and for vasoactive intestinal polypeptide and secretin. Prostaglandin E1 stimulation of hepatocyte adenylate cyclase was not additive to the stimulation caused by polypeptide hormones or catecholamines, nor did prostaglandin E1 decrease stimulation caused by these hormones. Although prostaglandin-sensitive adenylate cyclase was recovered with hepatocytes, 40 to 50% of the total liver prostaglandin-sensitive activity was recovered in a fraction of cell debris mixed with small cells which did not phagocytize colloidal iron.
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PMID:Stimulation of adenylate cyclase from isolated hepatocytes and Kupffer cells. 17 Dec 69

In dogs with acute experimental pancreatitis (AEP) induced according to Elliotts method the total, free and latent activity of lysosomal hydrolases (acid phosphatase, beta-glucuronidase and cathepsins) in whole homogenates and some subfractions of pancreas were studied. The animals were divided into three groups of 6 dogs each: I. control healthy dogs. II. AEP-treated with glucagon (0.33 mg of glucagon in drop infusion 3 times every six hours). III. AEP without any drug treatment. In dogs treated with glucagon the significant decrease of relative free activity of all tested hydrolases (66-80%) in comparison with the group without any treatment (III/80-90%) was found. Moreover significant decrease of total catheptic activity (about 1/3) in the former group was demonstrated. Incubation of lysosomal enriched fraction taken from group II/in medium buffered to pH 5.0 caused decreasing release of catheptic activity (60% of total) in comparison with the group III (75%). The histochemical reaction for acid phosphatase according to Gomoris method in pancreatic acinar cells of dogs treated with glucagon was less intensive than reaction in untreated animals. These results indicate on the less impairment of pancreatic lysosomes in AEP treated with glucagon in comparison with that in untreated animals.
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PMID:The lysosomal hydrolases in acute experimental pancreatitis in dogs treated with glucagon. 84 47

Prolonged starvation is known to induce significant alterations in several cardiac lysosomal enzymes, particularly the acid proteinase cathepsin D. To determine what specific factors might mediate these changes, fetal mouse hearts in organ culture were maintained in media designed to simulate selected hormonal or nutritional substrate changes that accompany starvation. Reduced concentrations of glucose caused an increase in the activity of beta-acetylglucosaminidase but had no effect on cathepsin D or acid phosphatase activites (i.e., effects opposite from those of starvation). Also, high concentrations of free fatty acid, acetoacetate, and beta-OH-butyrate induced an increase in cathepsin D (+18%) and a simultaneous decrease in glucosaminidase (-19%), with little change in acid phosphatase. Furthermore, glucagon had no effect on any of the enzymes, whereas growth hormone caused a small (6%) increase in cathepsin D activity. In addition, insulin deprivation caused significant increases (7-25%) in the activities of all three enzymes. Insulin deprivation and excess ketones, but not the other interventions, increased the proportion of enzyme activity which was nonsedimentable. These results suggest the possibility that lysosomal alterations during starvation may be related in part to prolonged insulin deficiency and exposure to high concentrations of ketones and free fatty acids.
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PMID:Hormonal and nutritional substrate control of cardiac lysosomal enzyme activities. 95 75

The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6-250 micrograms in a 0.5-ml reaction volume (1.7 X 10(-6) to 2.7 X 10(-5) M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250-micrograms dose, was 6.5-fold greater than control for insulin secretion and 6.7-fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5-250 micrograms, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100-micrograms dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33 micrograms) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33- and 100-micrograms doses thereafter. At the 11-micrograms dose significant stimulation of hormone release was observed only after a 4-h incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myelin basic protein stimulates insulin and glucagon secretion from rat pancreatic islets in vitro and in vivo. 170 May 78

Isolation and culture techniques for hepatocytes from whole livers of the cynomolgus monkey, Macaca fascicularis, are described. Hepatocytes were isolated by two-step perfusion of livers, using collagenase with hyaluronidase; fructose and trypsin inhibitor were included to reduce cell loss. Yields from a single liver average 4 X 10(9) cells with viabilities of 90.8 +/- 5.7%. Cells, plated on collagen substrates, were assessed for changes in morphology and various marker enzyme activities over a period of 7 d in culture. Cells exhibited a morphology similar to that observed for this species in vivo; little change in attached and spread cells was observed over the length of time monitored. Enzyme activities for catalase, succinate dehydrogenase, and tyrosine aminotransferase were observed to decrease significantly (though considerable activity remained), whereas acid phosphatase and 5'-nucleotide phosphodiesterase remained unchanged. Activity of cytochrome P-450 reductase was observed to increase slightly for the first 2 d, then decrease to about 60% of initial levels. Activity of alpha-mannosidase was stable for 4 d but was observed to be increased at Day 7. Cells were observed to retain metabolic responsiveness, demonstrated by glucose production by both gluconeogenesis and glycogenolysis in response to glucagon stimulation. The monkey hepatocytes obtained by methods described here thus retain hepatocellular morphology and activity through at least 1 wk in culture without medium or culture modification.
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PMID:Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca fascicularis). 197 77

The uptake and processing of glucagon into liver endosomes were studied in vivo by subcellular fractionation. After injection of [[125I]iodo-Tyr10]glucagon and [[125I]iodo-Tyr13]glucagon to rats, the uptake of radioactivity into the liver was maximum at 2 min (6% of the dose/g of tissue). On differential centrifugation, the radioactivity in the homogenate was recovered mainly in the nuclear (N), microsomal (P) and supernatant (S) fractions, with maxima at 5, 10 and 40 min, respectively; recovery of radioactivity in the mitochondrial-lysosomal (ML) fraction did not exceed 6% and was maximal at 20 min. On density-gradient centrifugation, the radioactivity associated first (2-10 min) with plasma membranes and then (10-40 min) with Golgi-endosomal (GE) fractions, with 2-5-fold and 20-150-fold enrichments respectively. Subfractionation of the GE fractions showed that, unlike the Golgi marker galactosyltransferase, the radioactivity was density-shifted by diaminobenzidine cytochemistry. Subfractionation of the ML fraction isolated at 40 min showed that more than half of the radioactivity was recovered at lower densities than the lysosomal marker acid phosphatase. Throughout the time of study, the [125I]iodoglucagon associated with the P, PM and GE fractions remained at least 80-90% trichloroacetic acid (TCA)-precipitable, whereas that associated with other fractions, especially the S fraction, became progressively TCA-soluble. On gel filtration and h.p.l.c., the small amount of degraded [125I]iodoglucagon associated with GE fractions was found to consist of monoiodotyrosine. Chloroquine treatment of [125I]iodoglucagon-injected rats caused a moderate but significant increase in the late recovery of radioactivity in the ML, P and GE fractions, but had little effect on the association of the ML radioactivity with acid-phosphatase-containing structures. Chloroquine treatment also led to a paradoxical decrease in the TCA-precipitability of the radioactivity associated with the P and GE fractions. Upon h.p.l.c. analysis of GE extracts of chloroquine-treated rats, at least four degradation products less hydrophobic than intact [125I]iodoglucagon were identified. Radio-sequence analysis of four of these products revealed three cleavages, affecting bonds Ser2-Gln3, Thr5-Phe6 and Phe6-Thr7. When GE fractions containing internalized [125I]iodoglucagon were incubated in iso-osmotic KCl at 30 degrees C, a rapid generation of TCA-soluble products was observed, with a maximum at pH 4. We conclude that endosomes are a major site at which internalized glucagon is degraded, endosomal acidification being required for optimum degradation.
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PMID:Fate of injected glucagon taken up by rat liver in vivo. Degradation of internalized ligand in the endosomal compartment. 226 96

To examine the function of islet lysosomal enzymes in islet hormone secretory mechanisms, we investigated the effects of the lysosomotropic drug chloroquine on islet lysosomal enzyme activities and basal as well as stimulated insulin and glucagon secretion. Chloroquine, added to islet homogenates, did not affect the activities of the lysosomal enzymes acid amyloglucosidase, acid alpha-glucosidase, or N-acetyl-beta-D-glucosaminidase. The activity of acid phosphatase, however, was inhibited at a high concentration of chloroquine (10(-3) M). When injected together with glucose, chloroquine (2 or 10 mumol/kg) inhibited the peak plasma insulin response. Similarly, at 24 hrs after chloroquine injection (100 mumol/kg), the plasma insulin response to glucose was reduced. In contrast, islets isolated from mice pretreated 24 hrs before with chloroquine, displayed glucose-stimulated insulin secretion in vitro that was not different from controls. Such islets showed, furthermore, enhanced activities of the enzymes acid phosphatase and neutral alpha-glucosidase but not of acid amyloglucosidase, acid alpha-glucosidase or N-acetyl-beta-D-glucosaminidase. Arginine-stimulated insulin response in vivo displayed a complex pattern; it was increased when arginine was injected together with chloroquine but decreased at 24 hrs after chloroquine administration. Arginine-stimulated glucagon secretion was not affected by chloroquine. We conclude that chloroquine pretreatment 24 hrs prior to glucose injection decreases glucose-stimulated insulin secretion in vivo by mechanisms that are not correlated to an inhibitory action on islet activities of glycogenolytic lysosomal enzymes.
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PMID:Islet hormone secretion and islet lysosomal enzyme activities in the mouse: effects of chloroquine. 307 44

The response of rat liver lysosomes to an intraperitoneal injection of glucagon has been evaluated from studies on the mechanical fragility, osmotic sensitivity, and sedimentation properties of these subcellular particles. It has been found that about (1/2) hr after the injection of glucagon the hepatic lysosomes exhibit a fairly sudden increase in their sensitivity to mechanical stresses and to exposure to a decreased osmotic pressure. At the same time, their sedimentation properties undergo complex changes characterized mainly by a significant increase in the sedimentation coefficient of a considerable proportion of the total particles. In addition, glucagon causes an increase in the proportion of slowly sedimenting particles, with the result that the distribution of sedimentation coefficients within the total population tends to become bimodal. The latter change is more pronounced for acid phosphatase, less so for cathepsin D, and barely detectable for acid deoxyribonuclease. All these modifications are maximal between 45 and 90 min after injection and regress to normal within approximately 4 hr. With the exception of the increase in the slow component, for which no explanation can be advanced at the present time, they are consistent with the hypothesis that glucagon causes an increase in lysosomal size, and may be related to the autophagic-vacuole formation known to occur after glucagon administration.
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PMID:Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. 429 15

Quantitative characterization of dense body, autophagic vacuole and acid phosphatase-bearing particle populations of rat liver have been made at 10 min intervals during the first 50 min following the intraperitoneal administration of glucagon. Beginning 10 to 20 min postinjection, increases in the number of autophagic vacuoles and in the osmotic sensitivity of acid phosphatase-bearing particles were observed, associated with a progressive disappearance of dense bodies. These changes appeared to reach a maximum 50 min after treatment. The average volume of autophagic vacuoles was found to be 440-870% greater than that of normal dense bodies during this time period. No consistent change in total acid phosphatase activity was noted. A detailed study of autophagic vacuole profile populations revealed the presence of five different types of profiles, two of which, types I and II, accounted for 76.3-94.4% of the profiles examined. Type I profiles primarily contained elements of the endoplasmic reticulum, free ribosomes, and ground cytoplasm. Type II profiles had mitochondrial profiles as their principal constituent, but endoplasmic reticulum and free ribosomes were also seen. At all time points type I profiles predominated, comprising 55-69% of the profiles found. Both profile types were bounded by single and double limiting membranes, the former being predominate. A time-dependent change in the ratio of single to double membrane-limited profiles could not be demonstrated. Morphometric parameters derived from profile size distributions indicated that the number of types I and II autophagic vacuoles increased with time, the rate being greater for the type II particle, except between 40 and 50 min. The average volume of the type II autophagic vacuole was consistently greater than that of the type I.
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PMID:Quantitative characterization of dense body, autophagic vacuole, and acid phosphatase-bearing particle populations during the early phases of glucagon-induced autophagy in rat liver. 432 60

Large amounts of glycogen accumulate in rat skeletal muscle fibers during the late fetal stages and are mobilized in the first postnatal days. This glycogen depletion is relatively slow in the immature leg muscles, in which extensive deposits are still found 24 hr after birth and, to some extent, persist until the 3rd day. In the more differentiated psoas muscle and especially in the diaphragm, the glycogen stores are completely mobilized already during the early hours. Section of the sciatic nerve 3 days before birth or within the first 2 hr after delivery does not affect glycogen depletion in the leg muscles. Neonatal glycogenolysis in rat muscle fibers takes place largely by segregation and digestion of glycogen particles in autophagic vacuoles. These vacuoles: (a) are not seen in fetal muscle fibers or at later postnatal stages, but appear concomitantly with the process of glycogen depletion and disappear shortly afterwards; (b) are prematurely formed in skeletal muscles of fetuses at term treated with glucagon; (c) contain almost exclusively glycogen particles and no other recognizable cell constituents; (d) have a double or, more often, single limiting membrane and originate apparently from flattened sacs sequestering glycogen masses; (e) are generally found to contain reaction product in preparations incubated from demonstration of acid phosphatase activity. The findings emphasize the role of the lysosomal system in the physiological process of postnatal glycogen mobilization and appear relevant in the interpretation of type II glycogen storage disease.
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PMID:Autophagic degradation of glycogen in skeletal muscles of the newborn rat. 433


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