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)

Acarbose is an alpha-glucosidase inhibitor which reversibly and competitively inhibits the digestion of oligo- and disaccharides at the brush border of the small intestine. This study evaluates the preventive and therapeutic properties of acarbose in the treatment of obesity. Dose-response experiments were performed during repeated sucrose loads in man in order to investigate the effects of acarbose on plasma insulin and blood glucose levels. After titration of efficient doses, a long-term tolerance test of acarbose was undertaken in a small pilot study. Finally, the relapse preventing effect of acarbose was tested during double-blind cross-over conditions in 24 weight reduced obese women. In growing Sprague-Dawley rats, the effects of acarbose on body weight, lipid depots and adipose tissue cellularity were tested during pair-feeding and ad libitum conditions. Such effects were also studied in adult ad libitum-fed rats. Blood glucose, plasma insulin, body fat, depot lipids as well as fat cell weight and number were determined with established techniques. During a sucrose load, acarbose reduced insulin in a dose-dependent fashion. Glucose was also reduced, but not dose-dependently and only to a moderate extent. During a 200 g sucrose load, 400 mg of acarbose did not necessarily result in a maximal reduction of the insulin response while the glucose response was maximally inhibited after 100 mg. Acarbose reduced the relapse rate after weight reduction. No serious side effects were observed. Flatulence and meteorism occurred frequently. In growing rats, acarbose retarded the development of body weight and of lipid depots not only during pair-feeding conditions but also in ad libitum-fed animals eating considerably more than their controls. The spontaneous food consumption was increased by acarbose also in adult rats but in these animals neither body weight nor lipid depots were significantly reduced by acarbose. It is concluded that acarbose induces a carbohydrate malabsorption. Insulin levels are reduced not only via a decreased glycemic stimulus but also by interference with other insulin releasing mechanism(s). Acarbose is the first drug ever tested with long-term relapse reducing effects after weight reduction. Animal experiments suggest that acarbose may be of value in the prevention of obesity, particularly since the drug retards lipid accumulation also during ad libitum-feeding.
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PMID:alpha-Glucosidase inhibition in obesity. 391 27

Nocturnal hypoglycemia is common in the diabetic patient on twice-daily regular and intermediate (NPH or lente) insulin regimens because intermediate-acting insulins before the main evening meal produce "unopposed" free insulin peaks around 0300 h, food absorption having been completed much earlier. Fourteen insulin-dependent diabetic patients were treated for 6 wk with the alpha-glucosidase inhibitor, acarbose, in a double-blind crossover study to see whether the drug would delay absorption of the evening meal sufficiently to correct the mismatch and prevent nocturnal hypoglycemia. On 200 mg acarbose (six patients), inhibition of carbohydrate digestion was so profound as to lead to midevening hypoglycemia with severe flatulence and abdominal colic. With a smaller dose of 100 mg before the evening meal (eight patients) there was a significant reduction in MAGE and MBG coupled with a clinically significant reduction in midevening and nocturnal hypoglycemic reactions. Alpha-glucosidase inhibition therefore provides a promising new approach to the problem of nocturnal hypoglycemia although a preparation that is safe for long-term clinical use remains to be found.
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PMID:A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition. 640 Jul 9

Acarbose, an alpha-glucosidase inhibitor, delays starch digestion and inhibits intestinal sucrase and maltase activity. Twenty-eight insulin dependent diabetics were given Acarbose (3 x 100 mg daily) over a two month period, preceded and followed by a two month placebo period. Acarbose reduced post-breakfast and post-dinner blood glucose values by 25% (p less than 0.001) and 24% (p less than 0.05) respectively. It also significantly reduced mean daily blood glucose by 18% (p less than 0.05) and mean amplitude of glycaemic excursions from 8.0 +/- 0.6 to 5.5 +/- 0.4 mmol/l (p less than 0.0005). Weight did not change significantly. Daily caloric and carbohydrate intake remained constant throughout the study while insulin requirements decreased slightly but significantly. Out of the 28 patients, 18 had absent while ten had slight residual B cell function as assessed by plasma C-peptide measurements. Treatment with Acarbose did not significantly affect residual B cell function. The beneficial effect of Acarbose on blood glucose control was seen in patients both with and without residual B cell secretion. The major side-effect was flatulence which was never severe enough to interrupt treatment, but led to a 50% reduction of the dose in one patient. It is concluded that Acarbose represents a useful additional means of improving metabolic control in insulin dependent diabetics.
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PMID:Improvement of metabolic control in insulin dependent diabetics treated with the alpha-glucosidase inhibitor acarbose for two months. 702 58

The influence of metronidazole on the breath hydrogen response and symptoms of sucrose malabsorption was investigated in a double-blind, randomized and controlled study. Carbohydrate malabsorption was induced by the competitive alpha-glucosidase inhibitor, acarbose. Metronidazole reduced flatulence and the breath hydrogen response during sucrose malabsorption without a change in intestinal carbohydrate absorption, as indicated by serum levels of gastric inhibitory polypeptide, serum insulin and blood glucose. The effect of metronidazole suggests that anaerobic bacteria mediate both signs and symptoms of the colonic response to sucrose malabsorption. In contrast to previous reports on lactose malabsorption, it was not possible to quantify sucrose malabsorption by comparing the breath hydrogen response to sucrose malabsorption with the H2 response to a lactulose load.
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PMID:Influence of metronidazole on the breath hydrogen response and symptoms in acarbose-induced malabsorption of sucrose. 716 May 49

The efficacy of the new intestinal alpha-glucosidase inhibitor, miglitol, and glibenclamide were compared in a 6-month double-blind controlled protocol involving 100 non-insulin dependent diabetic patients under diet alone. HbA1c levels (initially between 7 and 11%) were reduced (p < 0.05): -0.78 +/- 0.21% after miglitol and -1.18 +/- 0.20% after glibenclamide. The difference between the two treatments was not significant, although glibenclamide appeared to be more active than miglitol at 8 (p = 0.002) and 16 weeks (p = 0.01) but not at 24 weeks. Fasting glycaemia decreased after miglitol (8.7 +/- 0.3 vs 9.6 +/- 0.3 mmol/l, p = 0.005) and after glibenclamide (8.0 +/- 0.3 vs 9.1 +/- 0.3, p = 0.007). After miglitol, a decrease was noted after breakfast (p < 0.001) and lunch (p < 0.001). The same was true for glibenclamide (p = 0.004 and p < 0.001 respectively). A significant reduction in glucose incremental area during a standard meal test was noted at the end of miglitol (p = 0.008) or glibenclamide treatment (p = 0.04). Subgroups of nonresponders to both treatments were identified (10/49 with miglitol, 9/47 with glibenclamide). Side effects were recorded in 10 patients treated with miglitol (flatulence and meteorism, diarrhoea, 1 discontinued therapy) and in 10 treated with glibenclamide (asthenia, sensation of hunger). This study indicates that miglitol is suitable for initial application in diet-resistant Type 2 diabetic patients, providing, a persistent effect and acceptable side effects.
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PMID:Comparison of miglitol and glibenclamide in diet-treated type 2 diabetic patients. 755 6

Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic patients. It acts by competitively inhibiting the alpha-glucosidases in the intestinal brush border. The principal action of these enzymes is to convert nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g. glucose). Enzyme inhibitors delay this conversion, slowing the formation and consequently the absorption of monosaccharides, and thus reducing the concentration of postprandial blood glucose. Both starch and sucrose are influenced, whereas lactose and glucose are not. Many studies in experimental animals, healthy volunteers and patients with non-insulin-dependent diabetes mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose, with a lesser reduction of fasting blood glucose, plasma triglycerides and postprandial insulin levels. In long term studies in NIDDM patients, acarbose significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally absorbed from the gut and no systemic adverse effects have been demonstrated after long term administration. The drug allows undigested carbohydrates to pass into the large bowel where they are fermented causing flatulence, bloating and diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients, tend to decrease with time and seem to be dose-dependent. They are minimised by starting therapy with low doses (such as 50mg 3 times daily) which may be effective in many patients. An increase in serum hepatic transaminases observed in earlier studies in the US, where doses of acarbose up to 900mg daily were used, has been not reported with the lower doses of the drug actually recommended [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in patients with NIDDM when diet alone is no longer able to maintain satisfactory blood glucose control. Furthermore, it may be a valid alternative to sulphonylurea or biguanide therapy when these drugs are contraindicated and insulin administration may be delayed. Acarbose seems also to be a useful adjunct to hypoglycaemic oral agents but its precise role in this field has not been fully clarified.
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PMID:A risk-benefit appraisal of acarbose in the management of non-insulin-dependent diabetes mellitus. 772 53

We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +/- 0.99 micrograms/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3. 790 23

With alpha-glucosidase inhibitors generally improved metabolic control is achieved in NIDDM patients regardless of whether acarbose is administered in addition to other oral anti-diabetic agents or to diet alone. The most significant finding is the reduction of postprandial blood glucose concentrations. Long-term studies show a decrease in glycosylated haemoglobin and often also in fasting blood glucose levels. Placebo-controlled studies have proven that postprandial insulin concentrations are decreased under acarbose treatment while fasting plasma insulin is usually unchanged. The major side-effects of acarbose treatment involve the gastrointestinal system and include flatulence, abdominal discomfort and diarrhoea. Symptoms diminish with treatment time and are less severe when the treatment is started with low doses. Acarbose should usually be initiated as a 50 mg dose immediately before each major carbohydrate containing meal. Monotherapy with acarbose does not cause hypoglycaemia, however, hypoglycaemia may occur with combination of sulphonylurea or insulin treatment by the well-known reasons. In this case hypoglycaemia has to be treated by taking glucose.
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PMID:alpha-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. 800 25

To determine the prevalence of short polymers of glucose and starch malabsorption caused by small intestinal glucoamylase deficiency in children with chronic diarrhea, we studied small bowel biopsy specimens from 511 children (aged 1 month to 9 years) with chronic diarrhea evaluated at 54 medical centers. Glucoamylase and disaccharidase (lactase, sucrase, maltase, and palatinase) enzyme assays were performed. Of the 511 children, 15 had glucoamylase deficiency. Six who had significant small intestinal mucosal injury and disaccharidase deficiencies were defined as having secondary glucoamylase deficiency; the other nine patients with normal mucosal morphologic features were defined as having primary glucoamylase deficiency. Secretin tests showed normal pancreatic amylase values for age in all seven children tested. Four of them had abnormal findings on tolerance tests for starch and short polymers of glucose (rise in blood glucose concentration: < 20 mg/dl) and reducing substances in stools, and three of these four had symptoms of intolerance (abdominal distention, flatulence, and diarrhea). All seven patients responded to a starch elimination diet. After reintroduction of a starch diet, diarrhea recurred in four patients; this was alleviated 48 hours after reelimination of starch. We conclude that intestinal glucoamylase deficiency is present in some patients with chronic diarrhea.
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PMID:Small intestinal glucoamylase deficiency and starch malabsorption: a newly recognized alpha-glucosidase deficiency in children. 815 67

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted.
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PMID:The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. 854 34


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