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 glucose analogue 1-deoxynojirimycin (dNOJ) and some of its N-substituted derivatives have recently been described as potent inhibitors of the hepatic glycogenolysis induced by glucagon, Ca2+ ionophores or anoxia. The inhibition increased with time, in spite of a persistently high level of phosphorylase a [Bollen, M., Vandebroeck, A. & Stalmans, W. (1988) Biochem. Pharmacol. 37, 905-909]. dNOJ equilibrates within 1 min across the plasma membrane of hepatocytes. It is not phosphorylated or oxidized in the cell. The observation that dNOJ did not affect gluconeogenesis excludes the possibility that glucose-6-phosphatase is the target for the inhibition of glucose production from glycogen. Neither were the catalytic activities of phosphoglucomutase and phosphorylase a affected by the compound. dNOJ and two N-substituted derivatives inhibited instantaneously and completely the alpha-1,6-glucosidase activity of the debranching enzyme, with I50 values in the mumolar range. In contrast, the glucanotransferase activity of the latter enzyme was not inhibited by the compounds at 0.2 mM. The effect of dNOJ was further studied in an in vitro model system of glycogenolysis. The results were compatible with a block of glycogenolysis at the time when phosphorylase has removed the available glucosyl residues from the outer chains of the glycogen particles. This mechanism appears to account for the lag in the response of glycogenolysis to dNOJ.
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PMID:The antiglycogenolytic action of 1-deoxynojirimycin results from a specific inhibition of the alpha-1,6-glucosidase activity of the debranching enzyme. 252 91

Postprandial hyperglycemia in diabetic patients can be modified by delaying the digestion and/or absorption of dietary carbohydrates. We have studied an orally active alpha-glucosidase inhibitor, Bay 1099, in normal volunteers to determine whether these inhibitors can decrease postprandial rises in serum glucose without causing gastrointestinal symptoms or significant fecal caloric wastage. Six subjects were given 25, 50, or 100 mg of Bay 1099 or placebo before meals for 1 week, each with a 1-week washout period. Fasting and postprandial concentrations of glucose, insulin, glucagon, enteroglucagon, and gastrointestinal inhibitory peptide (GIP) were measured after the first and last dose of Bay 1099, and the fecal excretions of protein, fat, fiber, and total calories were measured on the last three days of each diet. The passage of unabsorbed carbohydrate into the colon was determined by breath hydrogen analysis three times during each study week. Increasing doses of Bay 1099 were found to decrease the postprandial rise in serum glucose concentration, delay the time to peak insulin concentration, and decrease the output of GIP after the meal. No adaptation was apparent after 1 week of therapy. A dose of inhibitor (50 mg tid), which greatly improves postprandial glucose and hormone output in diabetes, was associated with minimal symptoms and no excess fecal caloric losses. Thus, glucosidase inhibitors such as Bay 1099 may be useful in the management of patients with carbohydrate intolerance.
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PMID:Intestinal and metabolic responses to an alpha-glucosidase inhibitor in normal volunteers. 305 29

Beside intraluminal factors, humoral agents play an important role in intestinal adaptation. Enteroglucagon, the mucosal concentration of which is maximal in the terminal ileum and colon, is the strongest candidate for the role of small intestinal mucosal growth factor. The present experiment was designed to study the role of colonic enteroglucagon in stimulating mucosal growth in rats with a normal small intestine. After eight days of glucose large bowel perfusion, enteroglucagon plasma concentrations were 120.7 +/- SEM 9.2 pmol/l, versus 60.1 +/- 6.8 in mannitol perfused control rats (p less than 0.001). Gastrin, cholecystokinin, neurotensin, pancreatic glucagon, and insulin plasma concentrations were unchanged. Crypt cell proliferation, measured by the vincristine metaphase arrest technique, increased significantly in the small intestine of glucose perfused animals (p less than 0.005-0.001) in comparison with the controls. This resulted in a greater mucosal mass in both proximal and distal small bowel: mucosal wet weight, DNA, protein and alpha D-glucosidase per unit length intestine were all significantly higher (p less than 0.05-0.001) than in mannitol perfused rats. Our data, therefore, support the hypothesis that enteroglucagon is an enterotrophic factor and stress the possible role of the colon in the regulation of small bowel trophicity.
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PMID:Hyperenteroglucagonaemia and small intestinal mucosal growth after colonic perfusion of glucose in rats. 399 42

A 59-year-old Japanese farmer with asymptomatic fasting hypoglycemia and with exaggerated hypoglycemic episodes induced by insulin and oral hypoglycemic agent administered for his postprandial hyperglycemia was diagnosed as glycogen storage disease type I. This diagnosis was suggested by unresponsiveness of blood glucose level to glucagon and confirmed by 13% normal level of glucose 6-phosphatase activity in liver biopsy specimen and by the presence of PAS positive amylase digestable glycogen in liver specimen. This case was associated with an incomplete type of Fanconi syndrome characterized by hyperphosphaturic hypophosphatemia, partial aminoaciduria, mild proteinuria and hyperuricosuric normouricemia in spite of the lactic acidemia due to glycogen storage disease type I. The etiology for the absence of hypoglycemia and other typical manifestations of glycogen storage disease type I was studied. The glucose production from glycogen by lysosomal alpha 1,4-glucosidase especially at prolonged fasting and the presence of postprandial hyperglycemia by insulin deficiency are regarded as responsible for keeping this patient free from typical manifestations of glycogen storage disease type I.
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PMID:A case of glycogen storage disease type I associated with an incomplete type of Fanconi syndrome; the protective role of lysosomal alpha 1,4-glucosidase and insulin deficiency against hypoglycemia. 639 62

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.
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PMID:An electron microscopic and biochemical study of the effects of glucagon on newborn rat hepatocytes. 639 4

This study investigates the effect of Acarbose, a complex oligosaccharide of microbial origin with glucosidase-inhibiting properties in alimentary hypoglycemia secondary to rapid gastric emptying and in reactive hypoglycemia either isolated or associated with impaired glucose tolerance. Twenty-four patients complaining of symptoms suggesting hypoglycemia which occurred after meals and who showed blood glucose values of 2.5 mmol/l (45 mg/dl) or below on one or more occasions during a 5-h oral glucose tolerance test were selected and divided into three groups. Group I comprized seven patients with demonstrated rapid gastric emptying; group II comprized eight patients with impaired glucose tolerance, whereas the nine patients of group III were considered to present with "isolated reactive hypoglycemia" since they had a normal glucose tolerance and did not have either glycosuria or gastroduodenal pathology. All patients were submitted to two oral 75-g sucrose tolerance tests. Acarbose (100 mg) or placebo was ingested with the first drought of the sucrose solution administered in a randomized order. The investigation was performed in a double-blind manner. In all three groups Acarbose significantly reduced the magnitude of post-sucrose reactive hypoglycemia. The blood glucose nadir also occurred later, but this effect was statistically significant in group II only. In patients of groups II and III, such improvement of the glucose nadirs was preceded by a significant reduction of the post-sucrose glycemic peak. In all three groups, the insulin response to oral sucrose was reduced by Acarbose. Another consistent finding was the lack of sucrose-induced glucagon suppression when Acarbose was given. These data suggest that Acarbose might be a useful adjunct to the management of functional hypoglycemia.
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PMID:Acarbose in reactive hypoglycemia: a double-blind study. 669 57

A case of liver glycogen storage disease with amylo 1,6-glucosidase deficiency is reported. Enlarged liver was found at birth, and it is now accompanied by splenomegaly, low fasting blood glucose with ketonuria, elevation of transaminase values and glycogen accumulation with connective periportal tissue in liver histological study. In this glucogenosis results of functional tests on carbohidrate metabolism and glycogen enzymatic assay showed a direct relationship between functional and biochemical behaviour of liver cells. Amylo 1,6-glucosidase deficiency is accompanied by absence of glucogenolysis when glucagon is administrated after a long fast, and an increase of blood glucose when glucagon is administrated after food ingestion. Glycolisis tests show blood lactate elevation when some hexose or alanine are administrated; glyconeogenesis tests show blood glucose elevation when hexose, alanine or glycerol are administrated.
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PMID:[Glycogen storage disease by amylo 1,6-glucosidase deficiency (author's transl)]. 693 53

The effects of parenteral glucose, cyclic AMP and caffeine on the breakdown of glycogen in the lysosomes of newborn rat hepatocytes, were studied by using biochemical assays, electron microscopy and quantitative morphometry. Glucose prevented the normal postnatal increase in lysosomal volume, acid alpha 1,4 glucosidase activity and lysosomal glycogen breakdown. On the contrary, cyclic AMP and caffeine promoted this increase. There was a positive correlation between liver cyclic AMP concentration and acid glucosidase activity (R = 0.84, p < 0,001). Cyclic AMP also induced a change in the shape of lysosomes. The postulation that glucagon secreted after birth is the natural stimulus for the cyclic AMP-mediated postnatal increase in acid glucosidase activity and mobilization of the lysosomal glycogen in rat hepatocytes, is supported by these experimental findings.
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PMID:The breakdown of glycogen in the lysosomes of newborn rat hepatocytes: the effects of glucose, cyclic 3',5'-AMP and caffeine. 789 41

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.
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PMID:Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes. 800 23

The progress of knowledge relating to non-insulin-dependent diabetes mellitus (NIDDM) is associated with new therapeutic developments. Their different respective targets allow to classify them in drugs stimulating insulin secretion (glimepiride, repaglinide, glucagon-like peptide 1), medications reducing insulin resistance (thiazolidinediones) or in insulinmimetic agents (vanadium). Alpha glucosidase inhibitors, available in France since 1993, constitute another therapeutic approach, reducing postprandial hyperglycemia by delaying the digestion of complex carbohydrates. These new medications, safer and sometimes effective in a single daily administration, represent an alternative to classic oral antidiabetic agents allowing therapeutic combinations and a more global management of NIDDM.
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PMID:[New therapies in type 2 diabetes]. 978 90


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