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Frontiers in Endocrinology 2022The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy.... (Review)
Review
The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria and as well as suppress the potentially pathogenic bacteria . These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes actions on the gut microbiota.
Topics: Acarbose; Anti-Inflammatory Agents; Bacteria; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fatty Acids, Volatile; Glucagon-Like Peptide 1; Humans; Lactulose; Laxatives; Lipopolysaccharides; Peptides; Tyrosine
PubMed: 36187096
DOI: 10.3389/fendo.2022.956203 -
Scientific Reports Mar 2021To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The... (Clinical Trial)
Clinical Trial
The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).
To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.
Topics: Acarbose; Aged; China; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies
PubMed: 33649485
DOI: 10.1038/s41598-021-84015-0 -
Biomedical Journal Oct 2019In this study, gallic acid (GA) and its polymeric form-tannic acid (TA) which are two phenolic acids found abundantly distributed in plant food sources were investigated...
BACKGROUND
In this study, gallic acid (GA) and its polymeric form-tannic acid (TA) which are two phenolic acids found abundantly distributed in plant food sources were investigated for their influence on therapeutic properties of acarbose (AC) in vitro and in vivo in Drosophila melanogaster.
METHODS
Combinations of AC and GA or TA were assessed for their alpha-glucosidase and alpha-amylase inhibitory effects as markers of anti-hyperglycemic properties, as well as their free radicals scavenging, Fe chelating and malondialdehyde (MDA) inhibitory effects (in vitro). Furthermore, wild type D. melanogaster cultures were raised on diets containing AC, GA, TA and their various combinations for seven days. Thereafter, flies were homogenized and glucose concentrations, alpha-glucosidase and alpha-amylase activities, as well as reactive oxygen species (ROS) and total thiol levels were determined.
RESULTS
The results showed that GA and TA up to 5 mg/ml significantly (p < 0.05) increased the enzymes' inhibitory effects and antioxidant properties of AC in vitro. Also, there was significant reduction in glucose concentration, enzyme activities and ROS level in D. melanogaster fed diets supplemented with phenolic acids and acarbose.
CONCLUSIONS
These bioactive compounds-drug interactions provide useful information on improving the therapeutic properties of acarbose especially in its use as an antidiabetic drug.
Topics: Acarbose; Animals; Antioxidants; Drosophila melanogaster; Gallic Acid; Hypoglycemic Agents; Plant Extracts; Tannins; alpha-Amylases; alpha-Glucosidases
PubMed: 31783992
DOI: 10.1016/j.bj.2019.01.005 -
BMJ Open Diabetes Research & Care 2019Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including... (Comparative Study)
Comparative Study
OBJECTIVE
Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study was to observe the comparisons among those medications on gut microbiota composition.
RESEARCH DESIGN AND METHODS
Zucker diabetic fatty rats (n=32) were randomly divided into four groups, and had respectively gastric administration of normal saline (control), metformin (215.15 mg/kg/day), acarbose (32.27 mg/kg/day), or sitagliptin (10.76 mg/kg/day) for 4 weeks. Blood glucose levels were measured during an intragastric starch tolerance test after the treatments. 16S rRNA gene sequencing was used to access the microbiota in the fecal samples.
RESULTS
Metformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed by while was the dominant bacterium in the enterotype of the other three groups. The relative abundance of genera and was dramatically higher in acarbose group. Metformin and sitagliptin increased the relative abundance of genus Lactobacillus. Metagenomic prediction showed that the functional profiles of carbohydrate metabolism were enriched in acarbose group.
CONCLUSIONS
Metformin, acarbose and sitagliptin exerted different effects on the composition of gut microbiota and selectively increased the beneficial bacteria. Supplementation with specific probiotics may further improve the hypoglycemic effects of the antidiabetic drugs.
Topics: Acarbose; Animals; Bacteria; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Feces; Gastrointestinal Microbiome; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Male; Metagenomics; Metformin; RNA, Ribosomal, 16S; Rats; Rats, Zucker; Sitagliptin Phosphate
PubMed: 31641523
DOI: 10.1136/bmjdrc-2019-000717 -
The Journals of Gerontology. Series A,... Apr 2021Transcripts from noncoding repetitive elements (REs) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and...
Transcripts from noncoding repetitive elements (REs) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze REs in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that (a) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and high-fat diet (an age-accelerating treatment) increase RE expression; and (b) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Our results suggest that RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
Topics: Acarbose; Adolescent; Aged; Animals; Caloric Restriction; DNA Transposable Elements; Diet, High-Fat; Drugs, Chinese Herbal; Estradiol; Healthy Aging; Humans; Mice; Middle Aged; RNA, Untranslated; Repetitive Sequences, Nucleic Acid; Sirolimus; Young Adult
PubMed: 33257951
DOI: 10.1093/gerona/glaa302 -
Frontiers in Bioengineering and... 2021Acarbose is an effective anti-diabetic drug to treat type 2 diabetes mellitus (T2DM), a chronic degenerative metabolic disease caused by insulin resistance. The...
Acarbose is an effective anti-diabetic drug to treat type 2 diabetes mellitus (T2DM), a chronic degenerative metabolic disease caused by insulin resistance. The beneficial effects of acarbose on blood sugar control in T2DM patients have been confirmed by many studies. However, the effect of acarbose on patient kidney has yet to be fully elucidated. In this study, we report in detail the gene expression cascade shift, pathway and module enrichment, and interrelation network in acarbose-treated kidneys based on the in-depth analysis of the GSE59913 microarray dataset. The significantly differentially expressed genes (DEGs) in the kidneys of acarbose-treated rats were initially screened out by comparative analysis. The enriched pathways for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further identified. The protein-protein interaction (PPI) analysis for DEGs was achieved through the STRING database mining. Pathway interrelation and hub genes for enriched pathways were further examined to uncover key biological effects of acarbose. Results revealed 44 significantly up-regulated genes and 86 significantly down-regulated genes (130 significant differential genes in total) in acarbose-treated rat kidneys. Lipid metabolism pathways were considerably improved by acarbose, and the physical conditions in chronic kidney disease (CKD) patients were improved possibly through the increase of the level of high-density lipoprotein (HDL) by lecithin-cholesterol acyl-transferase (LCAT). These findings suggested that acarbose may serve as an ideal drug for CKD patients, since it not only protects the kidney, but also may relieve the complications caused by CKD.
PubMed: 34095098
DOI: 10.3389/fbioe.2021.659700 -
Pathogens and Global Health Oct 2023This study examines the effects of three different drugs with metformin, acarbose and pioglitazone active ingredients used for antidiabetic purposes on cysts and...
This study examines the effects of three different drugs with metformin, acarbose and pioglitazone active ingredients used for antidiabetic purposes on cysts and trophozoites. Cultures of trophozoites and cysts were prepared to test the anti-amoebic activity of metformin, acarbose and pioglitazone. Cultures were then prepared for cyst and trophozoite forms and parasites were exposed to different concentrations (0.750 mg/mL, 0.375 mg/mL, 0.186 mg/mL and 0.093 mg/mL) of metformin, acarbose and pioglitazone. As a result of the study, the reproductive potential suppressive effects and conversion from trophozoite form to cyst form of all three substances on trophozoites and cysts were determined. Parasites were counted at 12, 24 and 48 hours in the cell counter after staining with trypan blue. In comparison of the effects of metformin, acarbose and pioglitazone used in the study on trophozoites and cysts, it was observed that all three substances were statistically effective against cysts and trophozoites at a concentration of 0.750 mg/mL. Furthermore, it was determined that all concentrations of the three active substances included in the study significantly decreased the rate of cyst formation even at the end of the 7th day. In this context, it was determined that all three substances have amebicidal effects, and they significantly inhibit the transformation of trophozoites to cyst form. It is thought that these active substances, which are currently used as anti-diabetic, can be used in combination with other drugs in infections based on our study findings.
Topics: Animals; Trophozoites; Acanthamoeba castellanii; Hypoglycemic Agents; Acarbose; Pioglitazone; Metformin
PubMed: 36436006
DOI: 10.1080/20477724.2022.2151859 -
Nature Dec 2021The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search...
The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.
Topics: Acarbose; Amylases; Animals; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Inactivation, Metabolic; Metagenome; Models, Molecular; Mouth; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 34819672
DOI: 10.1038/s41586-021-04091-0 -
Heliyon Aug 2022Carbohydrate digestibility is a key determinant for elevated postprandial hyperglycemia (PPHG). Apart from dietary restrictions, one of the strategies to reduce PPHG is...
Carbohydrate digestibility is a key determinant for elevated postprandial hyperglycemia (PPHG). Apart from dietary restrictions, one of the strategies to reduce PPHG is to limit the activity of carbohydrate digestive enzymes within the gastrointestinal tract in order to reduce monosaccharide absorption rates. The present work aimed to assess the inhibitory capabilities of digestive enzymes (e.g., α-glucosidase and α-amylase) by anthoxanthins when used independently, in combination with acarbose, or with a different anthoxanthin. Our results showed that quercetin, myricetin, and luteolin presented lower IC values than acarbose and inhibited α-glucosidase through mixed-type inhibition. On the other hand, acarbose when compared with these anthoxanthins, remained the most potent inhibitor of α-amylase. Combinatorial treatment (i) acarbose-quercetin and (ii) myricetin-luteolin showed synergistic activity (CI value less than 0.9) in α-glucosidase inhibition. An additive effect (CI value between 0.9 and 1.1) in α-glucosidase inhibition was observed when acarbose-myricetin, acarbose-luteolin or when a combination of two different anthoxanthins (quercetin-myricetin and quercetin-luteolin) was used. This study suggests the potential use of anthoxanthins as functional food ingredients to mitigate PPHG towards the management of T2DM.
PubMed: 35991985
DOI: 10.1016/j.heliyon.2022.e10131 -
European Journal of Biochemistry Oct 2003Two inhibitors, acarbose and cyclodextrins (CD), were used to investigate the active site structure and function of barley alpha-amylase isozymes, AMY1 and AMY2. The... (Comparative Study)
Comparative Study
Two inhibitors, acarbose and cyclodextrins (CD), were used to investigate the active site structure and function of barley alpha-amylase isozymes, AMY1 and AMY2. The hydrolysis of DP 4900-amylose, reduced (r) DP18-maltodextrin and maltoheptaose (catalysed by AMY1 and AMY2) was followed in the absence and in the presence of inhibitor. Without inhibitor, the highest activity was obtained with amylose, kcat/Km decreased 103-fold using rDP18-maltodextrin and 10(5) to 10(6)-fold using maltoheptaose as substrate. Acarbose is an uncompetitive inhibitor with inhibition constant (L1i) for amylose and maltodextrin in the micromolar range. Acarbose did not bind to the active site of the enzyme, but to a secondary site to give an abortive ESI complex. Only AMY2 has a second secondary binding site corresponding to an ESI2 complex. In contrast, acarbose is a mixed noncompetitive inhibitor of maltoheptaose hydrolysis. Consequently, in the presence of this oligosaccharide substrate, acarbose bound both to the active site and to a secondary binding site. alpha-CD inhibited the AMY1 and AMY2 catalysed hydrolysis of amylose, but was a very weak inhibitor compared to acarbose.beta- and gamma-CD are not inhibitors. These results are different from those obtained previously with PPA. However in AMY1, as already shown for amylases of animal and bacterial origin, in addition to the active site, one secondary carbohydrate binding site (s1) was necessary for activity whereas two secondary sites (s1 and s2) were required for the AMY2 activity. The first secondary site in both AMY1 and AMY2 was only functional when substrate was bound in the active site. This appears to be a general feature of the alpha-amylase family.
Topics: Acarbose; Amylose; Binding Sites; Cyclodextrins; Enzyme Inhibitors; Glucans; Hordeum; Hydrolysis; Isoenzymes; Kinetics; Polysaccharides; Spectrophotometry; Structure-Activity Relationship; Substrate Specificity; alpha-Amylases
PubMed: 14511369
DOI: 10.1046/j.1432-1033.2003.03733.x