Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glucose-producing amylolytic activity in pancreatic islet tissue was characterized with regard to its properties with glycogen (amyloglucosidase) and maltose (maltase) as substrate, its optimum activity in islets from different strains of mice (NMRI, CBA and C-57BL) and after fasting, and its relation to the insulin secretory response after different secretagogues in vivo. Additionally the effects and fate of injected fungal acid amyloglucosidase were assessed. In the pancreatic islets of NMRI mice both the glycogen-splitting activity and the maltose-splitting activity displayed latency and an acid pH-optimum of about 5.0. After differential centrifugation a significant part of amyloglucosidase activity was found to be confined to the mitochondrial-lysosomal fraction. In crude islet homogenate the apparent Km for maltose at pH 5.0 was 2.1 mM. No Km for glycogen could be given because of complex kinetics in the presence of this substrate. The maltase activity was about 30% lower than the amyloglucosidase activity in islet tissue from NMRI mice. The reverse pattern was observed in the liver. Moreover, the liver amyloglucosidase activity was only one fourth of that of the islet tissue. The amyloglucosidase but not the maltase activity in islet tissue from CBA mice was lower than in islets from NMRI mice. Both activities were very low in islets from C-57 mice. A 24 hr fasting period reduced the amyloglucosidase but not the maltase activity in islets from NMRI mice. The insulin secretory response in vivo to an i.v. arginine load in the different strains and after fasting displayed the same pattern as the islet amyloglucosidase activity, whereas the insulin response following a glucagon injection was largest in the C-57 strain and unaffected by the fasting state. Pretreatment of mice with 0.05 mumol/kg of highly purified fungal amyloglucosidase, moderately (about 35%) enhanced the insulin secretory response to arginine, did not affect the response to glucagon, and greatly (about 100%) enhanced the response to glucose and tolbutamide. Moreover, treatment of mice with lysosomal stabilizers (glucocorticoids) reduced the insulin response to sulphonylureas and glucose, had no effect on the insulin response to beta-adrenergic and cholinergic stimulation, and increased ACTH-induced insulin release. A lysosomal labilizer (progesterone) enhanced the insulin response induced by glucose and tolbutamide.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Islet amyloglucosidase activity: some characteristics, and its relation to insulin secretion stimulated by various secretagogues. 308 68

Insulin has been proposed as an important factor in the regulation of growth and differentiation of the small intestine. In the newborn miniature pig, we induced significant physiologic increases in serum insulin and the insulin/glucagon ratio without altering serum glucose, beta-hydroxybutyrate, glucagon, cortisol, T3, and T4 using glucose-based total parenteral nutrition (TPN) in one group (group G) compared with a combination of glucose and fat in another group (group G/F). Control animals were sham-operated and fed a pelleted diet (group OC). Duodenal villus surface area and mucosal height were significantly greater in group G/F compared with group G. No other differences between the TPN groups were found in small intestinal growth, mucosal protein, deoxyribonucleic acid and ribonucleic acid content, and disaccharidase activities. As anticipated, group OC demonstrated increased intestinal length, weight, and villous surface area compared with the TPN groups. Ileal sucrase and jejunal and ileal maltase activities were greater in the TPN groups compared with those in group OC. Physiologic changes in serum insulin and the insulin/glucagon ratio induced by the TPN fuel mix do not appear to have altered small intestinal growth, composition, and differentiation in the healthy small intestine.
 ...
PMID:Effect of different total parenteral nutrition fuel mixes on small intestinal growth and differentiation in the infant miniature pig. 249 81

Glucagon is structurally related to secretin but inhibits the effects of secretin and cholecystokinin (CCK) on pancreatic secretion in vivo. Because secretin is a weak stimulant of pancreatic growth and potentiates the trophic effects of CCK, we hypothesized that glucagon might inhibit CCK-induced pancreatic growth. Four groups of 10 rats were injected with saline, glucagon (30 micrograms/kg, equimolar to a known trophic dose of secretin), cerulein (0.67 microgram/kg), or glucagon plus cerulein every 8 h for 5 days. The pancreas was excised, weighed, and assayed for total content of DNA, protein, amylase, chymotrypsinogen, and lipase. In control and glucagon-alone groups, the small intestine was also removed, weighed, and assayed for DNA, protein, and disaccharidase content. Glucagon alone decreased pancreatic DNA and increased lipase content. Compared with cerulein-treated animals, animals treated with glucagon and cerulein showed significant decreases in pancreatic weight and content of protein, amylase, and chymotrypsinogen. Although glucagon had significant effects on intestinal protein, maltase, and sucrase contents in certain segments, there was no clear pattern of response. The data suggest that glucagon may be an inhibitory regulator of pancreatic growth, acting to block the effects of CCK on pancreatic hypertrophy.
 ...
PMID:Glucagon inhibition of cerulein-induced hypertrophy of the exocrine pancreas. 336 38

Mechanisms of glycogenolysis have been investigated in a comparative study with Wistar rats and gsd rats, which maintain a high glycogen concentration in the liver as a result of a genetic deficiency of phosphorylase kinase. In Wistar hepatocytes the rate of glycogenolysis, as modulated by glucagon and by glucose, was proportional to the concentration of phosphorylase a. In suspensions of gsd hepatocytes the rate of glycogenolysis was far too high as compared with the low level of phosphorylase a; in addition, only a minor fraction of the glycogen lost was recovered as glucose and lactate, owing to the accumulation of oligosaccharides. When the gsd hepatocytes were incubated in the presence of an inhibitor of alpha-amylase (BAY e 4609) glycogenolysis and the formation of oligosaccharides virtually ceased; the production of glucose plus lactate, already modest in the absence of BAY e 4609, was further decreased by 40%, owing to the suppression of a pathway for glucose production by the successive actions of alpha-amylase and alpha-glucosidase. Evidence was obtained that gsd hepatocytes are more fragile, and that amylolysis of glycogen occurred in damaged cells and/or in the extracellular medium. This may even occur in vivo, since quick-frozen liver samples from anesthetized gsd rats contained severalfold higher concentrations of oligosaccharides than did similar samples from Wistar rats. However, administration of a hepatotoxic agent (CCl4) caused hepatic glycogen depletion in Wistar rats, but not in gsd rats. The administration of phloridzin and of vinblastine, which have been proposed to induce glycogenolysis in the lysosomal system, did not decrease the hepatic glycogen level in gsd rats. Taken together, the data indicate that only the phosphorolytic degradation of glycogen is metabolically important, and that alpha-amylolysis is an indication of an increased fragility of gsd hepatocytes, which becomes prominent when these cells are incubated in vitro.
 ...
PMID:An assessment of the importance of intralysosomal and of alpha-amylolytic glycogenolysis in the liver of normal rats and of rats with a glycogen-storage disease. 387 83

Although the purified porcine enteroglucagons glicentin and oxyntomodulin inhibit pentagastrin-stimulated gastrin acid secretion when given parenterally to rats, it is not known whether the postprandial rise in endogenous enteroglucagons is capable of exerting a similar effect. We have used the alpha-glucosidase inhibitor acarbose in combination with a sucrose- and starch-rich semisynthetic diet over 8 days to bring about a mean increase of 89 pmol/l in the fasting plasma enteroglucagon concentration in rats, without significantly affecting plasma gastrin concentrations. There was no significant suppression of pentagastrin-stimulated gastric acid secretion in the acarbose-treated rats, suggesting that endogenous enteroglucagons do not act as physiological inhibitors of gastric acid secretion.
 ...
PMID:Pentagastrin-stimulated gastric acid output and plasma enteroglucagon in acarbose-treated rats. 389 16

Acarbose, an alpha-glucosidase inhibitor, lowers the glycemic excursion following the ingestion of carbohydrates, in particular, sucrose. This was confirmed with increasing doses of acarbose (0, 50, and 100 mg) and the causes investigated. The absorption of the glucose moiety of sucrose was determined from plasma tracer concentrations when overnight-fasted normal subjects received a 100-g oral sucrose load labeled with sucrose [(1-14C]glucose and a simultaneous intravenous infusion of [3-3H]glucose. As the dose of acarbose given with the sucrose load was increased from 0 to 100 mg, the percentage of the load appearing in the peripheral circulation decreased from 90% to 62%. Malabsorption was confirmed by the appearance of breath hydrogen. Simultaneously, absorption time increased from 243 to 411 min. Maximal glycemic excursions were therefore lowered from 64 to 31 mg/dl. The plasma concentrations of gastric inhibitory polypeptide and insulin decreased with the acarbose dose so that the fractional disappearance rate of glucose also decreased. However, the concentrations of glucagon-like immunoreactivity (GLI) rose, confirming the ileal appearance of malabsorbed sucrose.
 ...
PMID:The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method. 636 57

Certain effects of glucagon administration on newborn rat hepatocytes were studied using biochemical assays, electron microscopy and quantitative morphometry. Glucagon accelerated the normal postnatal hyaloplasmic glycogen breakdown and the lysosomal glycogen breakdown. The glucagon-treated animals showed an increased activity of the enzyme, acid a 1,4 glucosidase (maltase). The results suggest that the catabolism of lysosomal glycogen is controlled by those agents that regulate the catabolism of hyaloplasmic glycogen and that this control is mediated through changes in the activity of the lysosomal acid a 1,4 glucosidases.
 ...
PMID:An electron microscopic and biochemical study of the effects of glucagon on newborn rat hepatocytes. 639 4

Jejunal mucosa of 6 d-old rats were cultured for 24 and 48 h in the presence of thyroxine, insulin, pentagastrin, glucagon, epidermal growth factor (EGF) or dibutyryl-A-3:5-MP cyclic with or without dexamethasone (DX). The enzymes were assayed on the purified brush borders. The various agents added alone to the basic culture medium had no effect with the exception of DX on the levels of enzyme activities. Dexamethasone alone induced sucrase, stimulated maltase, and protected other brush border enzyme activities (aminopeptidase, lactase, and alkaline phosphatase). When added to DX-supplemented medium, only the following factors modified the levels of enzymatic activities observed with DX alone. Insulin (10(-6) M) increased maltase, alkaline phosphatase, and lactase activity to a greater extent than DX at 24 h culture, the effect being maintained at 48 h on alkaline phosphatase only. At 48 h culture, both EGF (10(-8) M) and dbcAMP (10(-3) M) decreased DX-induced sucrase activity. The latter agent also depressed DX-stimulated aminopeptidase activity.
 ...
PMID:Organ culture of suckling rat intestine: comparative study of various hormones on brush border enzymes. 674 50

Glucagon is avidly degraded by the kidney, but the relative contribution of the luminal and basolateral tubular membranes to this process is unknown. We studied 125I-glucagon degradation by purified luminal (L) and basolateral (BL) tubular membranes prepared from rabbit kidney cortex, which showed enrichment vs. homogenate of marker enzyme activities (Na-K-ATPase for BL and maltase for L) of 10- and 14-fold, respectively. Renal homogenates and both tubular membrane fractions degraded glucagon avidly without reaching saturation even at pharmacologic concentration (10(-5) M) of the hormone. At physiologic concentration (3 x 10(-11) M) BL membranes degraded substantial amounts of glucagon (8.1 +/- 0.9 pg . micrograms protein-1 . h-1) even though at lesser rates (P less than 0.001) than the luminal fraction (33.3 +/- 1.9 pg . micrograms protein-1 . h-1). Competition experiments suggested that glucagon-degrading activity in both fractions includes both specific and nonspecific components, and the potency of different enzyme inhibitors to decelerate glucagon degradation was strikingly similar in the two membrane preparations. Glucagon degradation differed in several important aspects from the manner in which tubular membranes catabolize insulin, including absolute degradation rates and relative degrading capacity of the membranes vs. homogenates, both being substantially higher for glucagon. These results provide direct evidence that the renal metabolism of glucagon also involves its degradation by peritubular cell membranes.
 ...
PMID:Glucagon degradation by luminal and basolateral rabbit tubular membranes. 682 62

The present paper addresses the question how alpha-glucosidase inhibitors affect glucose homeostasis. To facilitate this already established data on the effects of induced malabsorption on gut hormones such as gastric inhibitory polypeptide (GIP) in connection with preliminary findings which deal with the new incretin hormone glucagon-like peptide 1 (7-36) amide (GLP-1) are discussed. To emphasize the possibly important impact of a regulated GLP-1 release in response to glucosidase inhibitor treatment we evaluate the recently introduced concept of 'glucose competence' of pancreatic beta-cells. The slowing of nutrient (i.e. glucose) absorption by therapeutic means (for example, acarbose) could supplement a new approach in the treatment of type 2 diabetics which would utilize the well-preserved insulinotropic activity of GLP-1 in these patients, its glucagon-lowering effect, and its possible inhibition of gastric emptying rates, the latter helping to reduce the requirement for rapid insulin secretory responses as is intended while using alpha-glucosidase inhibitor treatment.
 ...
PMID:Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes. 800 23


<< Previous 1 2 3 4 5 6 7 8 9 Next >>