Effects of the?-glucosidase inhibitor 1 desoxynojirimycin (BAY M 1099) on postprandial blood glucose, serum insulin and C-peptide levels in type II diabetic patients

Schnack, Ch.; Röggla, Georg; Luger, Anton; Schernthaner, Guntram

doi:10.1007/bf00607953

Cited by 28 publications

(7 citation statements)

References 3 publications

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“…This result was consistent with previous reports of miglitol significantly decreasing the postprandial insulin levels [9][10][11][12][13][14]. Serum insulin levels at 60 min after a meal were significantly decreased as compared with that in the control condition following miglitol administraton by intake schedules 1, 2 and 3 (42.0 ± 5.1, 26.7 ± 4.9, 21.0 ± 3.4 vs. 87.4 ± 11.3 µU/ml).…”

Section: Effects Of Miglitol Administered By Different Schedules On Tsupporting

confidence: 92%

Divided-Dose Administration of Miglitol just before and 15 Minutes after the Start of a Meal Smoothes Postprandial Plasma Glucose Excursions and Serum Insulin Responses in Healthy Men

2007

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Abstract. We recently demonstrated that administration of miglitol at 15 min after the start of a meal decreased the area under the curve (AUC) of plasma glucose, similar to the observation following its administration just before a meal. This finding prompted us to examine whether a divided-dose regimen of miglitol might attenuate postprandial glucose excursions even more effectively. We, therefore, examined several schedules of miglitol administration in 15 healthy men. Miglitol was administered by four different schedules in each subject (control: no miglitol, intake 1: drug administered just before a meal (50 mg); intake 2: drug administered at 15 min after the start of a meal (50 mg); intake 3: drug administered in two divided doses: just before a meal (25 mg) and at 15 min after the start of a meal (25 mg). The AUC of glucose excursions, defined as increment above the fasting glucose level, (AUC 0-180 min of glucose excursions) was significantly reduced as compared with that in the control condition after miglitol administration by intake schedule 3, while this parameter showed a tendency towards decrease after the drug administration by intake schedules 1 and 2. The AUC 0-180 min of the serum insulin level was also significantly decreased for all the intake schedules of miglitol, as compared with that in the control condition. Thus, administration of miglitol in two divided doses appeared to be the most suitable for obtaining effective regulation of postprandial glucose excursions in healthy men. This result may suggest that the divided-dose administration regimen may also be effective in diabetic patients.

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Section: Effects Of Miglitol Administered By Different Schedules On Tsupporting

confidence: 92%

Divided-Dose Administration of Miglitol just before and 15 Minutes after the Start of a Meal Smoothes Postprandial Plasma Glucose Excursions and Serum Insulin Responses in Healthy Men

2007

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“…This presumably is because of its predominant effect on intestinal sucrase (16), an effect comparable to that of acarbose (2)(3)(4)23). This finding agrees with the previous observations in normal humans (24) and subjects with NIDDM (17,(25)(26)(27). The more pronounced effect of BAYm 1099 on postprandial glycemia with the mixed food and sucrose test meal (TM3) is probably due to its combined inhibitory effect on various intestinal a-glucosidases.…”

Section: Discussionsupporting

confidence: 92%

Effects of BAYm 1099, New α-Glucosidase Inhibitor, on Acute Metabolic Responses and Metabolic Control in NIDDM Over 1 Mo

et al. 1988

Diabetes Care

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To examine the clinical role of BAYm 1099, 15 diet-treated non-insulin-dependent diabetic (NIDDM) subjects were randomized to start drug (50 mg 3 times/day) or placebo after a 4-wk run-in period in a double-blind crossover study. Treatment periods (4 wk) were separated by a 2-wk washout period. During the last week of each treatment period, three test meals (TMs) were administered: 60 g starch (TM1), 25 g sucrose (TM2), and combined 60 g starch and 25 g sucrose (TM3). Twelve subjects completed the study. The peak postprandial blood glucose, lactate, and pyruvate levels (means +/- SE) were significantly lower with active drug after all test meals, particularly TM2 (11.3 +/- 1.0 vs. 14.3 +/- 1.4 mM, P less than .001; 1.53 +/- 0.20 vs. 2.48 +/- 0.17 mM, P less than .001; and 105.1 +/- 17.6 vs. 147.6 +/- 11.1 microM, P less than) less than .001; and 105.1 +/- 17.6 vs. 147.6 +/- 11.1 microM, P less than .05, respectively. Peak blood glucose levels were significantly delayed. However, fasting blood glucose, HbA1, fructosamine, and cholesterol did not change during active treatment (10.0 +/- 1.0 vs. 9.9 +/- 1.0 mM, 10.0 +/- 0.7 vs. 9.4 +/- 0.7%, 2.44 +/- 0.10 vs. 2.37 +/- 0.07 mmol/100 g protein, and 6.7 +/- 0.3 vs. 6.5 +/- 0.3 mM, P NS). Flatulence and diarrhea were severe in 2 subjects, requiring termination of study. Thus, in NIDDM, BAYm 1099 was effective in diminishing and delaying postprandial excursions of blood glucose, lactate, and pyruvate after high- and low-sucrose meals, but overall metabolic control remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The observations in the present study could have important implications in the search for therapeutics for CMV. Although not yet fully determined, glucosidase inhibitors were well tolerated in animals (Saul et al, 1985) and man (Schnack et al, 1986;Joubert et al, 1986) and are of interest as potential antiviral agents. Also, the identification and characterisation of specific glycoproteins or their complexes which are associated with infectivity could provide the basis for a subunit vaccine.…”

Section: Discussionmentioning

confidence: 99%

Loss of cytomegalovirus infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis

et al. 1988

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Many plants contain polyhydroxyalkaloids which are potent inhibitors of glucosidases, enzymes involved in oligosaccharide trimming. These are important in determining the final configuration of specific glycoproteins. Human cytomegalovirus (CMV) encodes a number of glycoproteins, some of which ultimately reside in the outer envelope of the mature virion and are important for virus infectivity. Treatment with three polyhydroxyalkaloids, castanospermine (CAST), deoxynojirimycin (DNJ) and 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (DMDP) blocked the growth of infectious virus, as determined by yield reduction and plaque reduction assays. However, in the presence of CAST, CMV infected cells continued to shed virions into the extracellular medium, as determined by electron microscopy. Envelope glycoproteins of virions produced after treatment with CAST (2.5 mM) were immunoprecipitated with a monoclonal antibody (F5) specific for the gcI family of glycoproteins. Analysis by PAGE-SDS showed an absence of gcI complex 2 (gp52 disulphide-linked to gp130) with a proportional increase in gcI complex 1 (gp52 disulphide-linked to gp95). The results indicated that gp130 alone, or linked to gp52, was important for CMV infectivity. As well as being potential targets for antiviral agents against CMV, inhibitors of glycoprotein trimming reactions may define components of the virion surface important for infectivity.

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Effects of the?-glucosidase inhibitor 1 desoxynojirimycin (BAY M 1099) on postprandial blood glucose, serum insulin and C-peptide levels in type II diabetic patients

Cited by 28 publications

References 3 publications

Divided-Dose Administration of Miglitol just before and 15 Minutes after the Start of a Meal Smoothes Postprandial Plasma Glucose Excursions and Serum Insulin Responses in Healthy Men

Divided-Dose Administration of Miglitol just before and 15 Minutes after the Start of a Meal Smoothes Postprandial Plasma Glucose Excursions and Serum Insulin Responses in Healthy Men

Effects of BAYm 1099, New α-Glucosidase Inhibitor, on Acute Metabolic Responses and Metabolic Control in NIDDM Over 1 Mo

Loss of cytomegalovirus infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis

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