Acarbose Administration Research Articles

Clinical implications of dual therapy of acarbose plus myo-inositol on the thyroid profile in women with polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among PCOS women. Aims: To evaluate the benefits of acarbose plus myo-inositol therapy on the thyroid profile of PCOS. Methods: An open-labelled, parallel randomised clinical trial on 80 PCOS women based on inclusion and exclusion criteria was performed at the Department of Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur. Institutional ethics committee approval and prior informed consent were obtained. The trial was registered in CTRI (No: CTRI/2022/04/041877). Group A (n = 38) received metformin 500 mg TID, and group B (n = 39) received acarbose 50 mg TID along with myoinositol 1000 mg BID. Assessment of metabolic and hormonal profile was done at baseline and at the end of six months. Results: Both groups showed significant reductions in luteinising hormone (p <0.0001), total testosterone (p<0.05), thyroid stimulating hormone (p<0.05), fasting insulin (p<0.05), and homeostatic model assessment for insulin resistance (p<0.0001). The follicle-stimulating hormone was increased only in the metformin group. No significant changes in body mass index, free triiodothyronine, free tetraiodothyronine, and fasting glucose were observed in any group. Both therapies were safe, and no side effects or hypoglycaemia were recorded. Conclusions: In consideration of the beneficial effects of the study, we conclude that the administration of acarbose plus myo-inositol exerts positive effects on the thyroid and other endocrinological profiles in PCOS women.

Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

Acarbose, an α-Glucosidase Inhibitor, Maintains Altered Redox Homeostasis During Aging by Targeting Glucose Metabolism in Rat Erythrocytes.

Increasing age is the single largest risk factor for a variety of chronic illnesses. As a result, improving the capability to target the aging process leads to an increased health span. A lack of appropriate glucoregulatory control is a recurring issue associated with aging and chronic illness, even though many longevity therapies result in the preservation of glucoregulatory control. In this study, we suggest that targeting glucose metabolism to improve regulatory control can help slow the aging process. Male Wistar rats, both young (age 4 months) and old (age 24 months), were given acarbose (ACA) (30 mg/kg b.w.) for 6 weeks. An array of oxidative stress indicators was assessed after the treatment period, including plasma antioxidant capacity as determined by the ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (malondialdehyde [MDA]), reduced glutathione (GSH), total plasma thiol (sulfhydryl [SH]), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and sialic acid (SA) in control and treated groups. When compared with controls, ACA administration increased FRAP, GSH, SH, and PMRS activities in both age groups. The treated groups, on the contrary, showed substantial decreases in ROS, MDA, PCO, AOPP, AGE, and SA levels. The effect of ACA on almost all parameters was more evident in old-age rats. ACA significantly increased PMRS activity in young rats; here the effect was less prominent in old rats. Our data support the restoration of antioxidant levels in older rats after short-term ACA treatment. The findings corroborate the potential role of ACA as a putative calorie restriction mimetic.

Effect of Acarbose and olive leaf extract (Oleuropein) on Glycemic index and Antioxidant Status in High Fructose and H2O2 Exposed Rats (Parts-II)

This study was carried out to investigate the effect of acarbose or combination of acarbose and Oleuropein (OLEU) on glycemic index and antioxidant status of male rats exposed to high fructose(40%) and 0.05% hydrogen peroxide H2O2 Thirty-two adult male rats were randomly divided into four equal groups: control group (CC); T1( HFr-H2O2) group were exposed to high fructose (40%) in drinking water and given orally 0.05% H2O2; T2: 30mg/kg of acarbose were given orally to HF-H2O2 treated rats, while combination of acarbose and Oleuropein (50mg/kg. B.W) were given orally to (HFr-H2O2) treated rats in group T3. Blood samples were taken at zero time and after two months of the experiment for measuring some parameters related to glycemic index and antioxidant status. The results declared an elevation in the glycemic index (insulin and glucose concentrations and insulin resistance (IR)) and malondialdehyde (MDA) and depression in glutathione (GSH) concentrations in T1 group at the end of experiment comparing to other treated groups. Antioxidant status and glycemic index were restored after acarbose or combination of acarbose and Oleuropein treatment characterized by significant depression of serum glucose, insulin concentrations and IR, and alleviation of oxidative stress clarified by depression of serum MDA with elevation in serum GSH concentration in groups T2 and T3. On conclusion, the current study documented the oxidative and hyperglycemic effect of fructose and H2O2 that can be ameliorating by oral administration of acarbose. Besides, combination of OLUE supplement with acarbose possessed additive effects.

Diet supplemented with boiled unripe plantain (Musaparadisiaca) exhibited antidiabetic potentials in streptozotocin-induced Wistar rats.

The ameliorating effect and antidiabetic properties of diets augmented with boiled unripe plantain (20%-40%) in high fat fed/low dose of streptozotocin induced diabetic rats in comparison with the administration of acarbose were evaluated in this study using standard methods. High fat fed/low dose of streptozotocin (25 mg/kg body weight) was given to twenty-five male Wistar rats to induce diabetes leaving out 5 normal rats to serve as control. The animals were separated into five with six rats in each group and the experiment continued for 14 days. Investigations on the blood glucose concentration, enzymes (α-amylase, α-glucosidase, angiotensin I converting enzyme), thiobarbituric reaction substance (TBARS), High-density lipoprotein-cholesterol (HDL-c), and antioxidant status were determined. The findings revealed a rise in blood glucose level and the activities of α-amylase, α-glucosidase, angiotensin I converting enzyme, thiobarbituric reaction substance (TBARS) in untreated diabetic rats in group II while a reverse was observed in diabetic rats (Group IV and V) on exposure to diets augmented with boiled unripe plantain. The obtained overall results in diet treated groups are similar to that of acarbose treated groups. The untreated diabetic rats (Group II) exhibited contrary results of the biochemical assays. This finding showed that boiled unripe plantain can provide the therapeutic measures that needed to be further explored as possible future economic means of managing diabetes in developing nations. PRACTICAL APPLICATIONS: As diabetes has been implicated to disrupt various pathways involved in the metabolism of macromolecules, there are proposed adoptive methods of preventing them among which is the inhibition of starch hydrolyzing enzymes, increasing the enzymatic antioxidant status and prevention of lipid peroxidation, Plantain by-product which is known as an inexpensive food can be prepared to manage the condition of diabetes in patients. Our former in vitro findings have revealed the bioactive contents of unripe plantain product which has been further explored in vivo to experiment is nutritional benefits. The study therefore proposes that unripe plantains, when boiled, can provide the necessary natural therapeutic measures to be considered as a potential economic means of managing diabetes in underdeveloped countries.

Acarbose Potentially Binds to the Type I Peptide Deformylase Catalytic Site and Inhibits Bacterial Growth: An In Silico and In Vitro Study.

In bacteria, peptide deformylase (PDF), a metalloenzyme, removes N-formyl methionine from a nascent protein, which is a critical step in the protein maturation process. The enzyme is ubiquitously present in bacteria and possesses therapeutic target potential. Acarbose, an FDA-approved antidiabetic drug, is an alpha-glucosidase inhibitor of microbial origin. Clinical studies indicate that acarbose administration in humans can alter gut microbiota. As per the best of our knowledge, the antibacterial potential of acarbose has not been reported. The present study aimed to check the binding ability of acarbose to the catalytic site of E. coli PDF and assess its in vitro antibacterial activity. Molecular docking, molecular dynamic (MD) simulation, and MM-PBSA experiments were performed to study the binding potential of the catalytic site, and a disc diffusion assay was also employed to assess the antibacterial potential of acarbose. Acarbose was found to form a hydrogen bond and interact with the metal ion present at the catalytic site. The test compound showed a better docking score in comparison to the standard inhibitor of PDF. MD simulation results showed energetically stable acarbose-PDF complex formation in terms of RMSD, RMSF, Rg, SASA, and hydrogen bond formation throughout the simulation period compared to the actinonin-PDF complex. Furthermore, MM-PBSA calculations showed better binding free energy (ΔG) of acarbose PDF than the actinonin-PDF complex. Moreover, acarbose showed in vitro antibacterial activity. Acarbose forms conformational and thermodynamically stable interaction with the E. coli peptide deformylase catalytic site. Results of the present work necessitate in-depth antimicrobial potential studies on the effect of acarbose on drug resistance and nonresistant bacteria.

An integrated chemo-informatics and in vitro experimental approach repurposes acarbose as a post-ischemic neuro-protectant.

The online version contains supplementary material available at 10.1007/s13205-022-03130-5.

Sargassum fusiforme polysaccharide partly replaces acarbose against type 2 diabetes in rats

The objective of present research was to explore whether Sargassum fusiforme polysaccharide (SFP) could partly replace acarbose against type 2 diabetes in rats. Results indicated that SFP co-administered with low-dose acarbose intervention typically mitigated diabetic symptoms and serum profiles and exhibited better anti-diabetic effects than single acarbose treatment in controlling fasting blood glucose, improving insulin resistance and mitigating kidney injuries. The RT-qPCR analysis indicated that SFP co-administered with low-dose acarbose administration distinctly activated the IRS/PI3K/AKT signaling pathway compared with single acarbose treatment. Moreover, the co-administration also restrained liver fat accumulation via affecting the expression of HMGCR and SREBP-1c genes. In addition, the 16S rRNA gene sequencing analysis indicated that SFP co-administered with low-dose acarbose significantly restored beneficial composition of gut flora in diabetic rats, such as the increase of Muribaculaceae, Lachnospiraceae, Bifidobacterium, Ruminococcaceae_UCG-014, Ruminococcus_1, Romboutsia, Eggerthellaceae, Alistipes and Faecalibaculum, and the decrease of Escherichia-Shigella. These results suggested that SFP, the novel natural adjuvant of acarbose, displayed the desirable benefits in minimizing the dose of drug, while improving the anti-diabetic efficiency.

Acarbose bioequivalence: Exploration of eligible protocol design.

Acarbose is a poorly absorbed α-glucosidase inhibitor that acts locally in the intestinal tract. Therefore, the evaluation of its bioequivalence (BE) should be based on pharmacodynamic (PD) rather than pharmacokinetic (PK) endpoints. Currently, there is no consensus on the best method for acarbose BE evaluation. The optimal protocol design regarding dosing time/dose and PD parameters requires further exploration. The aim of the study was to identify an optimum protocol for establishing acarbose BE in healthy Chinese volunteers using PD endpoints. Three pilot studies were conducted in healthy Chinese subjects. Study 1 was an open, randomized, two-period crossover study using the reference (R) drug at the dose of 1×50mg. Study 1 aimed to determine appropriate dosing time by comparing the PD effect of acarbose between two administration methods. One method was concomitant administration of sucrose and acarbose, and another method was acarbose administration 10min before sucrose. Study 2 was an open, randomized, three-period crossover study. Subjects were given the R drug at the dose of 1×50mg, 2×50mg or 3×50mg in a random sequence. The aim of Study 2 was to identify a reasonable dose of acarbose in the BE study. Study 3 was conducted with an open, randomized, three-period crossover design using the test (T) or R drug in an R-T-R sequence at the dose of 2×50mg. Study 3 aimed to compare the BE between the R and T drug and determine intra-individual variation. Twelve subjects were recruited in Study 1, Study 2 and Study 3, respectively, with a one-week washout period. Serum glucose and insulin concentrations were determined after sucrose administration (baseline) and sucrose/acarbose co-administration. In Study 1, no significant differences in PD parameters were found between the two administration methods. The results of Study 2 revealed that the optimal dose was between 1×50mg and 2×50mg. The comparison of PD parameters indicated that the rectifying method could distinguish between different formulations. Study 3 showed that the geometric mean ratios of Cmax, r , AUC0-2 h, r and AUC0-4 h, r were 90.06%, 84.55% and 84.21%, respectively, using the rectifying method. The 90% CIs of Cmax, r were within acceptance limits (80.00%-125.00%), whereas that of AUC0-2 h, r and AUC0-4 h, r were out of the range. The intra-individual variation was approximately 21% for R formulation. Based on the variation, the number of subjects needed to identify formulation differences in the pivotal study would be 55 with 90% power at the 5% level of significance. The results from our study manifested that a randomized, balanced, two-way crossover design was eligible to evaluate acarbose BE. The appropriate dosing time was concomitant administration of sucrose and acarbose, and the optimal dose was 2×50mg. The rectifying method exhibited preferable sensitivity and applicability in acarbose BE evaluation. A practical sample size of the pivotal study would be 55. These results may help to provide new insights into the protocol design of acarbose BE study.

Novel Short-Clustered Maltodextrin as a Dietary Starch Substitute Attenuates Metabolic Dysregulation and Restructures Gut Microbiota in db/db Mice.

Molecular structure of starch in daily diet is closely associated with diabetes management. By enzymatically reassembling α-1,4 and α-1,6 glycosidic bonds in starch molecules, we have synthesized an innovative short-clustered maltodextrin (SCMD) which slowly releases glucose during digestion. Here, we investigated the potential benefits of the SCMD-containing diet using diabetic db/db mice. As compared to a diet with normal starch, this dietary style greatly attenuated hyperglycemia and repaired symptoms associated with diabetes. Additionally, in comparison with acarbose (an α-glucosidase inhibitor) administration, the SCMD-containing diet more effectively accelerated brown adipose activation and improved energy metabolism of db/db mice. Furthermore, the SCMD-containing diet was a more suitable approach to improving the intestinal microflora than acarbose administration, especially the proliferation of Mucispirillum, Akkermansia, and Bifidobacterium. These results reveal a novel strategy for diabetes management based on enzymatically rebuilding starch molecules in the daily diet.

Protective effects of acarbose against insulitis in multiple low-dose streptozotocin-induced diabetic mice

AimsThe development of type 1 diabetes is associated with inflammatory lesion of the pancreatic islets, known as insulitis. In this study, we focused on the protective effects of acarbose against insulitis in streptozotocin (STZ)-induced diabetic mice and the underlying mechanisms. Main methodsThe mouse models were established via intraperitoneal injection of multiple low-dose STZ. Blood glucose level and body weight were measured. The severity of insulitis and inflammatory parameters in pancreatic tissues were evaluated. Insulin levels in pancreas and serum were also assessed. In vitro, MIN6 β cells were exposed to pro-inflammatory cytokines to assess the protective effects of acarbose. Cell function and apoptosis were evaluated. Key findingsWe found that acarbose administration by gavage reduced the severity of insulitis and improved insulin levels in the experimental diabetic mice. ELISA revealed decreased levels of the inflammatory response markers IL-1β and TNF-α in mouse pancreatic tissues following acarbose treatment. In vitro, acarbose increased cell viability, decreased cell apoptosis, and improved GSIS in MIN6 β cells exposed to pro-inflammatory cytokines. In addition, caspase-3 level and p-p53/p53 ratio in β cells were reduced by acarbose treatment. SignificanceTaken together, these results revealed a novel function of acarbose in attenuating insulitis. The protective effects of acarbose elicited in vitro and in vivo were shown to be mediated, at least in part, through its anti-inflammatory action.

English

Tetrapleura tetraptera and Aframomum citratum fruits are used as spices and in the traditional pharmacopeia in Cameroon. They are mostly combined and preheated for many purposes while cooking. The effects of roasting on the phenolic content of spices, phenolic profile of a beverage made with the mix of roasted spices and its hypoglycaemic activity on diabetes complications were investigated. Aqueous extract (infusion: 100°C; 1/5 g/ml) was prepared, and the total polyphenols and flavonoids contents before and after heat treatment were quantified. Four formulations of T. tetraptera/A. citratum (95/5; 90/10; 85/15; 80/20) were assessed and the in vitro glucose adsorption capacity of the extracts was studied to retain the most effective formulation (AEF). Phenolic and derivatives compounds of AEF were analysed using HPLC-DAD methodology. The AEF hypoglycaemic activity (250 mg/kg bw) and the various complications of hyperglycaemia after Streptozotocin induction (55 mg/kg) were examined on rats. Significant (p<0.05) improvements in phytochemical content were noticed for T. tetraptera and AEF extracts after heat treatment. Among the phenolic compounds identified, flavone, protocatechic, chlorogenic, p-Coumaric acids, and naringin showed the highest concentrations. Significantly, the effect of AEF is the same as the administration of AEF-Glibenclamide (Glibenclamide) and Acarbose after 4 h when assessing the anti-hyperglycaemic test. The influence of Glibenclamide (the reference drug) is significantly improved by AEF, and this synergy has the best anti-hyperglycaemic, hypoglycaemic, hypotriglyceridaemic potential and boosts catalase, superoxide dismutase activities while reducing Malondialdehyde (liver, pancreas, haemolysates) and hydroperoxide (liver, plasma, and kidney) contents compared with the use of single AEF. Key words: Tetrapleura tetraptera, Aframomum citratum, anti-diabetic, hyperglycaemia, roasting, pharmacopeia, hypoglycaemia, infusion, HPLC-DAD, Streptozotocin &nbsp

Evaluation of the Effects of Acarbose on Weight and Metabolic, Inflammatory, and Cardiovascular Markers in Patients with Obesity and Overweight.

Background:Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease and type 2 diabetes. The aim of this study is to assess the effects of acarbose as an antihyperglycemic agent (drug) on late complications of MetS.Methods:This double-blind randomized clinical trial was done on patients with MetS admitted to Isfahan Endocrine and Metabolism Research Center. They were assigned randomly to two groups: A who received acarbose (n = 32) and group B who received a placebo (n = 42) for 6 months. Cardiovascular indexes including flow-mediated dilation (FMD), intima-media thickness (IMT), epicardial fat thickness (EFT), and C-reactive protein (CRP) were measured at baseline and 6 months after the treatment and compared between the two groups.Results:Post-intervention mean of weight (mean difference: −2.5 ± 0.89) and abdominal obesity (mean difference: −2.2 ± 0.64) in acarbose group were significantly decreased (P value < 0.001). High-density lipoprotein (HDL) level in acarbose group was significantly higher than control group (44.7 ± 7.6 vs 41.1 ± 6.4; P value = 0.043), while the other metabolic parameters were not significantly different between the two groups (P value > 0.05). In both groups, CRP and EFT decreased significantly after the intervention, and the levels of CRP, EFT, and IMT markers in the acarbose group were significantly lower than control group (P value < 0.05).Conclusions:The administration of acarbose in patients with MetS can decrease weight and abdominal obesity as well as the reduction of inflammatory and cardiovascular markers, including CRP, EFT, and IMT and also increases HDL.

Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats

ObjectiveRecent 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...

Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones.

Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.

Hypoglycemic and hypolipidemic effects of samnamul (shoot of Aruncus dioicus var. kamtschaticus Hara) in mice fed a high-fat/high-sucrose diet.

The hypoglycemic and hypolipidemic effects of samnamul were investigated. The α-glucosidase inhibitory activity of samnamul in vivo was determined in normal mice. Oral administration of samnamul extract (500mg/kg) or acarbose (50mg/kg) significantly reduced the postprandial glucose response. The effects of chronic consumption of samnamul on fasting hyperglycemia and dyslipidemia were determined in C57BL/6J mice with diabetes mellitus induced by a high-fat/high-sucrose (HFHS) diet. Consumption of samnamul extract at 0.5% of the diet for 12weeks decreased serum glucose, triglyceride, and cholesterol levels, the homeostasis model assessment for insulin resistance index, and activities of maltase and sucrase in the small intestine. These results suggest that samnamul had hypoglycemic and hypolipidemic effects in an animal model of type 2 diabetes and that the hypoglycemic effect occurred partly via the inhibition of α-glucosidase activity.

Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice.

Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway.

Colitis microscópica atípica: descripción de 2 casos de colitis colágena, uno con células gigantes y otro con seudomembranas

We describe two patients with symptoms of microscopic colitis, which microscopically showed collagenous colitis (CC) with atypical features. A 54-year-old patient complained of watery diarrhea following the administration of acarbose for type-2 diabetes, which disappeared after drug withdrawal on two occasions. The colon biopsies showed collagenous colitis containing multinucleated giant cells. A 60-year-old woman with a 3year history of watery diarrhea underwent colonic biopsies which showed CC with pseudomembranes. The possible etiology of these two atypical variants of microscopic colitis, one of CC with giant cells induced by acarbose and the other of CC with pseudomembranes, is discussed.

Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model

Psoriasis is a chronic autoimmune disease of undefined etiology that involves dysregulated interplay between immune cells and keratinocytes. Acarbose was found to decrease inflammatory parameters in diabetic patients in addition to its anti-diabetic effects. Here, we report that imiquimod (IMQ)-induced epidermal hyperplasia and psoriasis like-inflammation were significantly inhibited by acarbose treatment. Real-time PCR showed that mRNA levels of the cytokines TNF-α, IL-6, IL-1β IL-17A, and IL-22 in skin were also decreased significantly by acarbose. In addition, we found that acarbose reduced infiltration of CD3+ T cells and GR-1+ neutrophils in lesional skin and also reduced the percentage of IL-17-producing CD4+ T cells (Th17) and IL-17- and IL-22-producing γδ T cells in the spleen. In contrast, acarbose increased the frequency of IL-10-producing CD4+ regulator Tr1 T cells in the spleen and small intestine. These results indicate that oral administration of acarbose can attenuate the severity of imiquimod-induced psoriasis with local and systemic anti-inflammatory and immune modulation effects, thus suggesting that acarbose is an effective therapeutic strategy for psoriasis regulation.

Effects of Miglitol, Acarbose, and Sitagliptin on Plasma Insulin and Gut Peptides in Type 2 Diabetes Mellitus: A Crossover Study.

IntroductionBoth dipeptidyl peptidase-4 inhibitors and α-glucosidase inhibitors (α-GI) have been reported to change the incretin and insulin secretion. To examine the effects of acarbose, miglitol, and sitagliptin on glucose metabolism and secretion of gut peptides, we conducted a crossover study in patients with type 2 diabetes mellitus (T2DM).MethodsEleven Japanese patients with T2DM underwent four meal tolerance tests with single administration of acarbose, miglitol, sitagliptin, or nothing. Fasting and postprandial plasma levels of glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were measured.ResultsEarly-phase insulin secretion was reduced following acarbose and miglitol, and the areas under the curve (AUC) of insulin at 180 min following acarbose and miglitol were significantly lower than sitagliptin. AUC of plasma glucose at 180 min after acarbose, miglitol, and sitagliptin tended to be lower than in controls, and plasma glucose levels at 30–60 min following miglitol were significantly lower than in controls. Plasma glucagon, ghrelin, and des-acyl ghrelin levels did not differ among the four conditions. Postprandial plasma active GLP-1 levels and AUC of GLP-1 increased significantly in both the sitagliptin and miglitol groups compared to control. Postprandial plasma total GIP levels increased following sitagliptin but decreased after acarbose and miglitol. Changes in incretin levels tended to be greater with miglitol than acarbose.ConclusionThese results showed that sitagliptin and α-GIs, miglitol more so than acarbose, improved hyperglycemia in patients with T2DM after single administration, and had different effects on insulin and incretin secretion.Trial registration: UMIN-CTR number, UMIN000009981.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-015-0113-3) contains supplementary material, which is available to authorized users.