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)

In blind studies the effects of a new alpha-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.
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PMID:The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man. 37 42

Acarbose, an alpha-glucosidase inhibitor, delays absorption of carbohydrate in the gut, thereby lowering postprandial glucose levels. Safety data on this drug have been gathered in a series of studies on animals and in extensive clinical trials in humans. Although an initial long term feeding study in rats showed an excess of renal tumours at very high dosages of acarbose (up to 300 mg/kg bodyweight daily), further evaluation with similar studies in rats, hamsters, and dogs indicated that the problem was related to carbohydrate malabsorption. With adequate glucose intake and in gavage studies, no difference in tumour incidence between placebo- and acarbose-treated groups was seen. From 1976 to 1989, safety data on acarbose were obtained in approximately 8800 patients in 2 separate groups of clinical trials, the Bayer International Clinical Data Pool and the American phase III trials. Almost all adverse experiences, as reported by 56 to 76% of patients on acarbose vs 32 to 37% of patients on placebo, were related to the digestive system and included diarrhoea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. In the American trials a small but significant increase in liver transaminases was seen, 3.8% in acarbose-treated patients vs 0.9% in controls together with a 1% increase in anaemia in the acarbose group. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable.
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PMID:Safety profile of acarbose, an alpha-glucosidase inhibitor. 128 May 77

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

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

Two studies of the new alpha-glucosidase inhibitor, miglitol, in patients with non-insulin-dependent diabetes mellitus (NIDDM) are reported. In the first, 13 patients, poorly controlled on sulphonylureas, received miglitol 50mg three times daily for 4 weeks. Post-prandial blood glucose was reduced after breakfast, lunch, and tea compared with placebo (p less than 0.05-0.01) but there was no improvement in fasting blood glucose, serum fructosamine or haemoglobin A1. In a dose-response study the effect of a single dose of miglitol (0,50,100,150 or 200mg) on post-prandial glycaemia after a test breakfast was assessed in 20 patients with mean +/- SEM fasting blood glucose 9.9 +/- 0.4 mmol/l. With 50mg miglitol, there was a significant reduction in blood glucose from 30 to 120 min post-prandially compared with placebo. Increasing doses of miglitol further depressed the post-prandial rise in blood glucose and with 200mg there was no significant change from fasting levels. Side-effects were limited to flatus and loose stools particularly with the higher doses but were not severe. Miglitol effectively reduces post-prandial blood glucose rise in NIDDM with as little as 50mg but there is considerable individual variation. Larger doses may be necessary in patients already poorly controlled on sulphonylureas.
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PMID:Alpha glucosidase inhibition in the treatment of non-insulin-dependent diabetes mellitus. 296 27

Peptide YY (PYY) is a recently discovered peptide found in the distal ileum and colon. It circulates in plasma and concentrations rise in malabsorptive conditions. The potential of PYY as an indicator of impaired carbohydrate digestion was studied in a pharmacological model of intestinal glucosidase inhibition. Thirteen type-2 diabetics on long-term treatment with the alpha-glucosidase inhibitor acarbose (3 x 100 mg per day) had test meals with and without acarbose 100 mg before and after the treatment period (mean 46 weeks), a test meal with acarbose after 20 weeks of continuous treatment and a final test meal without acarbose 6 weeks after cessation of treatment. Without acarbose mean plasma PYY concentrations rose from a mean basal value of 11.5 +/- 2.9 pmol/l to 19.5 +/- 3.9 pmol/l 120 min postprandially (P less than 0.01). Acarbose treatment did not effect basal plasma PYY concentrations but significantly enhanced food stimulated PYY concentrations acutely, at 20 weeks and at the final treatment test meal. Mean incremental integrated plasma responses (area under curve) rose by 183%, 184% and 169%, respectively (P less than 0.05). After cessation of treatment postprandial responses returned to pretreatment values within 6 weeks. Conversely, the integrated incremetal postprandial plasma responses of glucose and insulin were reversibly reduced by acarbose to 58% +/- 9% and 60% +/- 10% of controls, respectively. Self-assesed side effects of flatulence and more frequent bowel action showed no regular relationship to the PYY response. PYY seems to act as an indicator of the increased carbohydrate load to the distal intestine even in the absence of clinical symptoms. It may contribute to the hypoglycaemic effect of alpha-glucosidase inhibitors by slowing down intestinal transit.
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PMID:Peptide YY in diabetics treated chronically with an intestinal glucosidase inhibitor. 305 80

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.
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PMID:Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. 328 12

Retardation of meal carbohydrate absorption by inhibition of starch degradation improves glucose tolerance in normal and diabetic humans. To determine the effects of Bay-m-1099, a new alpha-glucosidase inhibitor, on insulin requirements and prandial glucose tolerance in patients with insulin-dependent diabetes mellitus (IDDM), plasma glucose, triglyceride, and free insulin concentrations were measured after ingestion of a standard breakfast, lunch, and dinner in nine patients with IDDM in a single-blind, randomized, crossover design. A 20% reduction in insulin was given 30 minutes before the meals when the subjects received Bay-m-1099 (50 mg). This resulted in the AUC for plasma insulin to be significantly less with Bay-m-1099 (AUC, 8.2 +/- 1.3 vs. 12.8 +/- 1.6 microU/ml/min with placebo; P less than 0.01). Despite this reduction in plasma insulin levels, postprandial plasma glucose concentrations were reduced for the breakfast (73 +/- 15 vs. 112 +/- 14 mg/dl/min with placebo; P less than 0.01) and dinner (23 +/- 8 vs. 4 +/- 1 mg/dl/min with placebo; P less than 0.05) meal with Bay-m-1099. Bay-m-1099 did not affect postprandial plasma triglycerides and was well tolerated, the major side effect being flatulence (4/9) and mild diarrhea (4/9). We conclude that inhibition of intestinal alpha-glucosidases by Bay-m-1099 in IDDM reduces meal insulin requirements by at least 20% and that such an agent could be useful in the management of diabetes mellitus by reducing hyperinsulinemia.
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PMID:A new alpha-glucosidase inhibitor (Bay-m-1099) reduces insulin requirements with meals in insulin-dependent diabetes mellitus. 331 50

1. alpha-Glucosidase inhibitors delay carbohydrate absorption and have been proposed as adjunctive therapy for diabetes mellitus. 2. To determine the effects of two new alpha-glucosidase inhibitors, Bay-m-1099 and Bay-o-1248, on meal carbohydrate and lipid tolerance, plasma glucose, insulin and triglyceride levels were measured at 15-60 min intervals over 12 h after ingestion of a standard breakfast, lunch and dinner of identical composition in 31 normal volunteers. 3. The volunteers were randomized to receive either Bay-m-1099 (50 or 25 mg) or placebo prior to each meal, or the single administration of Bay-o-1248 (20 or 10 mg) or placebo prior to breakfast. 4. Only Bay-m-1099 at the 50 mg dose reduced significantly the postprandial increase in plasma insulin levels after each meal when compared with placebo (25, 36, 54% at breakfast, lunch, and dinner, respectively; P less than 0.05). Both drugs were well tolerated, with side effects limited to complaints of flatulence. 5. Thus, with the dosage schedule employed, Bay-m-1099, but not Bay-o-1248, significantly reduced postprandial increments in plasma insulin.
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PMID:The effect of two new alpha-glucosidase inhibitors on metabolic responses to a mixed meal in normal volunteers. 332 89

BAYo1248 and BAYm1099 are two new alpha-glucosidase inhibitors. Postprandial glucose tolerance was significantly improved and postprandial insulin requirements were significantly reduced as compared to placebo after breakfast and lunch when 20 mg BAYo1248 were administered prior to breakfast and after breakfast, lunch and dinner when 50 mg BAYm1099 were given prior to all three main meals. Postprandial breath H2 concentrations were mildly increased when these alpha-glucosidase inhibitors were given and no patient complained of any adverse effects (such as flatulence, abdominal pain or diarrhea). BAYo1248 and BAYm1099 might be useful adjuncts to insulin in the treatment of patients with insulin-dependent diabetes mellitus.
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PMID:Effects of two new alpha-glucosidase inhibitors on glycemic control in patients with insulin-dependent diabetes mellitus. 352 Jan 33


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