Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha-glucosidase inhibitor acarbose induces a reversible delay of carbohydrate digestion. This action represents a new therapeutic option for the treatment of diabetes mellitus. The current investigation is a prospective, randomized double-blind crossover trial in 24 non-insulin dependent diabetics, fairly well controlled on diet alone or diet plus sulphonylurea. In periods of 10 weeks, the patients received successive treatment with acarbose and placebo in random order. A significantly lower HbA1 level and urinary glucose excretion were shown during acarbose as compared to placebo. The other parameters of diabetic control remained unchanged. Acarbose induced no significant alterations in the concentrations of important electrolytes, iron, vitamin B12 and folic acid. Although no major side effects occurred, meteorism and flatulence were frequent complaints. These data suggest that acarbose, in a dosage of 3 x 100 mg/day, is a safe drug, with slight beneficial effect on diabetic metabolic control.
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PMID:Effects of acarbose on carbohydrate metabolism, electrolytes, minerals and vitamins in fairly well-controlled non-insulin-dependent diabetes mellitus. 177 45

In two randomized, placebo-controlled, double-blind studies, the efficacy, duration of action and tolerability of a single morning dose of 25, 50, and 100 mg miglitol (BAY m 1099), an absorbable inhibitor of intestinal alpha-glucosidases, were assessed after repetitive sucrose or maize-starch loads (50 g of carbohydrates in 400 ml of water each at 08.00, 12.00, and 17.00 h). With sucrose, miglitol reduced the postprandial rise in blood glucose, serum insulin and serum gastric inhibitory polypeptide concentrations at any dosage. This effect was dose-dependent and confined to the first carbohydrate load in the morning, thus indicating the duration of alpha-glucosidase inhibition of less than 4 h. Sucrose malabsorption, indicated by breath hydrogen responses, occurred dose-dependently with 50 and 100 mg, but not with 25 mg of miglitol. Similarly, symptoms of carbohydrate malabsorption were absent with 25 mg of the inhibitor and mild to moderate after 50 and 100 mg of miglitol. With starch as the substrate, BAY m 1099 led to a significant amelioration of glycemic and hormonal rises after the first meal, but not thereafter. A numerical dose dependency was recognized, but this was not significant at the 5% level. Symptoms of carbohydrate malabsorption were absent with 25 mg and negligible with 50 mg BAY m 1099, but occurred almost regularly with the 100-mg dose. Breath hydrogen concentrations increased gradually with the dose of miglitol administered. A single morning dose of 25-100 mg of miglitol thus may be useful for the control of postprandial hyperglycemia after breakfast. Due to the duration of action of less than 4 h, this substance should be given with the three main meals.
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PMID:Inhibition of glycemic and hormonal responses after repetitive sucrose and starch loads by different doses of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in man. 178 28

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the alpha-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers. 181 67

Post-prandial glucose excursions remain elevated in most patients with diabetes even when normal fasting plasma glucose levels have been achieved. In 39 patients with type 2 diabetes who had attained basal normoglycaemia by therapy with diet alone, a sulphonylurea, a basal insulin supplement or basal plus prandial insulin the mean glycosylated haemoglobin (HbA1) values were at the upper end (mean +/- 1SD, 8.1 +/- 1.1%) of the normal range (5.0-8.2%). Miglitol, an alpha-glucosidase inhibitor, given in a dose of 50 mg three times a day was studied in a double blind randomized crossover study. In diet and sulphonylurea treated patients, a mean 25% reduction of the post-prandial plasma glucose excursions was obtained whereas in ultralente treated patients miglitol appeared to reduce basal plasma glucose levels (p < 0.006). Side effects were limited to minor gastrointestinal disturbances, usually ameliorating after the first week of therapy. Alpha-glucosidase inhibition to prevent post-prandial glycaemia may have a role in patients in whom sulphonylurea or diet therapy has been used to obtain normal basal glucose concentrations.
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PMID:Post-prandial glycaemic reduction by an alpha-glucosidase inhibitor in type 2 diabetic patients with therapeutically attained basal normoglycaemia. 184 49

Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.
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PMID:Effect of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor, on glucose, insulin, C-peptide and GIP responses to an oral sucrose load in patients with post-prandial hypoglycaemic symptoms. 188 80

Caco-2 cells, which express spontaneous enterocytic differentiation at confluency, is one of the most relevant in vitro models for the study of differentiation and regulation of intestinal functions. However, these cells are normally cultured in the presence of 15-20% serum which renders extremely complex the identification of the factors involved in the regulation of both proliferation and differentiation. This study has been devoted to the establishment of chemically defined culture conditions which can sustain growth and differentiation of Caco-2 cells. The replacement of serum by ITS (insulin, transferrin, and selenium) allowed for normal structural and functional differentiation of cells as revealed by the establishment of cell polarity and the expression of brush-border membrane enzyme markers (sucrase, maltase, lactase, alkaline phosphatase, gamma-glutamyltransferase, aminopeptidase N, and dipeptidyl-dipeptidase IV), although the levels of sucrase activity were lower in ITS-supplemented medium. Coating petridishes with either type IV collagen or basement membrane proteins (Matrigel) did not improve the differentiation of cells, brush-border membrane enzyme activities being, in fact, lower when the cells were grown on these substrata. When triiodothyronine (T3, 5 x 10(-8) M) was added to the ITS-supplemented medium, disaccharidase and alkaline phosphatase activities were significantly increased while gamma-glutamyltransferase activity was diminished by T3 and stimulated by epidermal growth factor (1.6 x 10(-6) M). On the other hand, hydrocortisone (HC, 10(-6) M) did not modify disaccharidase and peptidase activities. These data clearly show that Caco-2 cells can be maintained in serum-free medium and that this system allows the study of the factors involved in the regulation of the differentiation of enterocyte in vitro.
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PMID:Caco-2 cells cultured in serum-free medium as a model for the study of enterocytic differentiation in vitro. 193 45

Inhibition of intestinal alpha-glucohydrolase activity is one approach for reducing the glycemic response from dietary carbohydrate and may prove useful for the treatment of diabetes mellitus. In this article, we describe the pharmacological properties of a time-dependent intestinal alpha-glucohydrolase inhibitor, MDL 73945. When preincubated 2 h with a rat intestinal mucosa preparation before substrate addition, MDL 73945 was a potent inhibitor of sucrase, maltase, glucoamylase, and isomaltase activities (MDL 73945 concentrations required to cause a 50% decrease in enzyme activity, 2 x 10(-7), 1 x 10(-6), 5 x 10(-6), and 8 x 10(-6) M, respectively); without preincubation, it was 10- to 500-fold less potent. In rats, a single oral dose of MDL 73945 administered simultaneously with 2 g/kg body wt sucrose resulted in a dose-dependent reduction in the area under the 0- to 3-h glycemic response curve, which was significant at 1 (45% reduction) and 3 (65% reduction) mg/kg. When administered 1 h before sucrose, the compound was more potent, with 0.3 mg/kg MDL 73945 significantly reducing the glycemic response to sucrose by 62%. A reduction in the glycemic response to sucrose was accompanied by reduced insulin secretion. MDL 73945 was slightly less effective against a starch load, with 3 and 10 mg/kg MDL 73945 administered 0.5 h before starch reducing the glycemic response by 39 and 52%, respectively. MDL 73945 was more effective against a sucrose load in streptozocin-administered rats than in control rats and was as effective after 16 daily doses as after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New potent alpha-glucohydrolase inhibitor MDL 73945 with long duration of action in rats. 206 Jul 19

To further document the effect of insulin on intestinal maturation, suckling rats were treated either with exogenous insulin (12.5 mU.g body wt, intraperitoneally, twice daily) or with saline from d 8 to 12 postpartum. Sucrase activity in brush border membrane extracts was precociously induced by insulin, whereas the activities of other brush border membrane enzymes (maltase, aminopeptidase, and neutral lactase) were enhanced (+ 30 to + 131%, p less than 0.01 versus controls). The lysosomal enzyme, N-acetyl-beta-glucosaminidase, which normally declines at weaning was significantly (p less than 0.025) decreased in both villus (-51%) and crypt cells (-57%) isolated from the jejunum of insulin-treated rats. The microsomal enzyme, sulfatase C, and the cytosolic enzyme, lactate dehydrogenase, were also sensitive to insulin with decreases in activity ranging from -37 to -63% (p less than 0.05) compared to saline-treated control rats. Insulin at doses of 0.5 or 12.5 mU did not influence plasma total corticosterone levels, which were about 9-fold lower in suckling than in 25-d-old weaned rats. In weaned rats (from d 25 to 32) insulin treatment (12.5 mU) failed to influence the activity of brush border membrane hydrolases or of lysosomal, microsomal, and cytosolic enzymes. The synthesis rate of mature sucrase-isomaltase, measured in weaned rats (32 d) by the incorporation of 14C-leucine into the enzyme precursor protein, was equivalent in both groups. These data demonstrate that the immature enterocyte of the suckling rat is responsive to insulin, whereas the mature enterocyte of the weaned rat is unresponsive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of the rat small intestine: responsiveness of villus and crypt cells to insulin during the suckling period and unresponsiveness after weaning. 217 34

This double-blind study was performed to evaluate the relation of the glycemic and hormonal (insulin, gastric inhibitory polypeptide) responses to standardized starch and sucrose meals to signs (H2 exhalation) and subjective symptoms of carbohydrate malabsorption during administration of 100 mg BAYm 1099 (miglitol) t.i.d. over a period of 8 weeks. Two groups of 8 male healthy volunteers received either placebo or verum. Oral sucrose loading tests (50 g) with and without miglitol were performed at day -5, 1, 25 and 53 of the study, starch loading tests (50 g) with and without the inhibitor were carried out at day -2, 4, 28 and 56. Miglitol significantly flattened the glycemic responses to sucrose and starch without evidence of diminished efficacy over the 8-week period. Also the blunting effect of miglitol on serum insulin and gastric inhibitory polypeptide responses and the stimulation of breath hydrogen exhalation proving carbohydrate malabsorption with starch and sucrose remained unchanged over time. Comparing breath hydrogen exhalation, responses were more pronounced after sucrose than after the starch loading tests. Symptoms (bloating, flatulence, diarrhea, cramps) were merely noticeable with starch as the substrate, but clearly present after sucrose. These symptoms were substantially curtailed during continuous drug intake. It is concluded that - irrespective of the substrate (starch/sucrose) - there is no escape of the desired effects of alpha-glucosidase inhibition by miglitol over 8 weeks, but symptoms of gaseousness due to carbohydrate malabsorption may undergo habituation.
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PMID:Postprandial glycemic control, hormonal effects and carbohydrate malabsorption during long-term administration of the alpha-glucosidase inhibitor miglitol. 229 49

The influences of glucose, the benzothiadiazide derivative diazoxide (an inhibitor of insulin release), and the potent non-glucose insulin secretagogue 3-isobutyl-1-methylxanthine (IBMX) on insulin secretion and the activities of 3 different lysosomal enzymes were studied in isolated mouse islets. We found that the increase in insulin secretion during a 4 hr incubation period in the presence of 16.7 mM glucose was accompanied by an increase in islet activities of the lysosomal enzymes acid amyloglucosidase and acid alpha-glucosidase. These alpha-1,4-glucoside splitting enzyme activities were increased by 45-55% (p less than 0.01). No influence by glucose was encountered for the activities of N-acetyl-beta-D-glucosaminidase or the non-lysosomal neutral alpha-glucosidase. Upon incubation with 0.2 mM diazoxide and glucose (16.7 mM) the glucose-induced insulin secretion was markedly suppressed and no significant increase in islet lysosomal enzyme activities was observed. On the other hand, insulin secretion induced by IBMX to the same magnitude as with 16.7 mM glucose, was accompanied by an increase in islet activity of N-acetyl-beta-D-glucosaminidase (p less than 0.05), whereas no apparent changes in acid amyloglucosidase and acid alpha-glucosidase activities could be detected. In conclusion, the determination of lysosomal enzyme activities in isolated mouse islets revealed that glucose was able to induce an increased activity of glucose producing glycogenolytic acid hydrolases under conditions when a concomitant insulin secretion occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin secretion and lysosomal enzyme activities in isolated mouse islets. Effects of glucose, diazoxide and isobutylmethylxanthine. 243 78


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