Disease relevance of acarbose

• Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial [1].
• A 58-year-old man with diabetes mellitus was treated with acarbose 300 mg daily [2].
• The most frequent side-effects to acarbose treatment were flatulence and diarrhoea [1].
• Low dose acarbose without symptoms of malabsorption in the dumping syndrome [3].
• We report a case of lymphocytic colitis induced by acarbose [4].

Psychiatry related information on acarbose

• However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027) [5].
• Adjunctive treatment with acarbose (possibLy together with sulphonylurea or insulin treatment) can be effectively utilised to achieve blood glucose control if postprandial hyperglycaemia is a problem and cannot be sufficiently controlled by dietary modifications [6].
• 3. Acarbose at both dosages was associated with phenotype-specific alterations in food intake amount and feeding pattern, resulting in an attenuation of age-associated increases in food intake [7].

High impact information on acarbose

• 13 days after the start of treatment with acarbose, generalised erythema multiforme developed with blood eosinophilia [2].
• A challenge test for acarbose confirmed allergic reaction clinically and histologically [2].
• The aim of the present experiments was to investigate the fate and effects of acarbose along the small intestine using a slow-marker perfusion technique [8].
• Recovery of acarbose during 4 h was 65% +/- 9% (mean +/- SEM) of ingested dose in the ileum but 94% +/- 9% in the jejunum, indicating that the compound was neither degraded nor absorbed by the intestine to a major degree [8].
• Acarbose reduces the absorption of monosaccharides derived from dietary carbohydrates, which play an important role in the metabolism and toxicity of some chemical compounds [9].

Chemical compound and disease context of acarbose

• The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development [10].
• When mice received a standard diet, acarbose had no effect on body weight, blood glucose or insulin levels [11].
• Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo [12].
• Current strategies are aimed at amelioration of insulin resistance (diet, exercise, weight loss, and metformin and troglitazone therapy), augmentation of insulin supply (sulfonylurea and insulin therapy), or limitation of postprandial hyperglycemia (acarbose therapy) [13].
• This multicenter, double-blind, placebo-controlled study compared the efficacy and safety of diet alone, acarbose, tolbutamide, and acarbose-plus-tolbutamide in non-insulin-dependent diabetes mellitus (NIDDM) patients [14].

Biological context of acarbose

• Acarbose did not influence fasting blood glucose, food intake, or the normal development of obesity in the mice [15].
• The pseudotetrasaccharide acarbose has high affinity for the active site (Ki,app = 1 microM) and low affinity for a secondary site (Kd = 2.3 mM) in barley alpha-amylase 1, distinguished by inhibition kinetics and spectral perturbation [16].
• In the structure of TLGT complexed with acarbose, the inhibitor was bound at the cleft within domain I, indicating that domain I is a catalytic domain of TLGT [17].
• In the acarbose group, subjects carrying the minor G allele of rs4253776 and the CC genotype of rs4253778 of PPARA had a 1.7- and 2.7-fold increased risk for diabetes [18].
• The putative biosynthetic gene cluster for the alpha-glucosidase inhibitor acarbose was identified in the producer Actinoplanes sp. 50/110 by cloning a DNA segment containing the conserved gene for dTDP-D-glucose 4,6-dehydratase, acbB [19].

Anatomical context of acarbose

• The pseudotetrasaccharide acarbose inhibits pancreatic islet glucan-1,4-alpha-glucosidase activity in parallel with a suppressive action on glucose-induced insulin release [20].
• Basal (non insulin-stimulated) glucose uptake, which is decreased in isolated soleus muscle from untreated obese mice, returned to normal values under acarbose treatment [11].
• Treatment with Acarbose did not significantly affect residual B cell function [21].
• One of the most striking features of the acarbose-treated rats was the reduction of adipose tissue weight due to a reduced adipocyte size [22].
• Exocrine and endocrine pancreatic function were studied simultaneously in the isolated perfused pancreas from rats fed a normal or an acarbose-containing diet (150 mg/100 g food) for 20 days [23].

Associations of acarbose with other chemical compounds

• Male Sprague-Dawley rats were kept on a daily ration (20 g) of powdered chow diet containing 0, 20, 40, or 80 mg/100 g of acarbose, with drinking water containing 0% or 10% of ethanol (vol/vol) [9].
• We studied the effects of acarbose on the hepatotoxicity of carbon tetrachloride (CCl4) and acetaminophen (AP) in rats, both of which exert their toxic effects through bioactivation associated with cytochrome P450 2E1 (CYP2E1) [9].
• Randomized, prospective clinical trials have documented the benefits of thiazolidinediones, metformin, and acarbose in combination with insulin [24].
• Clinical trials have demonstrated that lifestyle changes (e.g., diet and exercise) as well as use of metformin, acarbose, or troglitazone reduce the incidence of type 2 diabetes [25].
• We examined the effect of acarbose (n = 4), glibenclamide (n = 6), and placebo (n = 6) on insulin and leptin levels during 24-h periods before and after 16 weeks of therapy [26].

Gene context of acarbose

• The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption [27].
• Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release [27].
• Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02) [28].
• To probe the interactions of acarbose with other carbohydrate recognition enzymes, the crystal structure of E. coli maltodextrin phosphorylase (MalP) complexed with acarbose has been determined at 2.95 A resolution and refined to crystallographic R-values of R (Rfree) = 0.241 (0.293), respectively [29].
• GIP plasma concentrations (increasing with placebo from approximately 10 to approximately 85 pmol/l and with acarbose to approximately 55 pmol/l (P < 0.0001) and their integrated responses were significantly lowered (by 43%) by acarbose (P = 0.021) [30].

Analytical, diagnostic and therapeutic context of acarbose

• Fate and effects of the alpha-glucosidase inhibitor acarbose in humans. An intestinal slow-marker perfusion study [8].
• We performed peptide mapping analysis to identify the protected Trp residues, and Trp321, Trp337, Trp433, and Trp569 were identified as candidates to be protected by acarbose [31].
• Titration of placebo/acarbose is well described in the protocol and in the study design paper [5].
• PATIENTS AND METHODS: Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo [12].
• This multicenter double-blind study compared the efficacy and safety of acarbose with placebo in the treatment of obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) managed by diet [32].

References