Postprandial Hyperglycemia Research Articles

Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting α-glucosidase

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia, which play crucial roles in the management of type 2 diabetes. Protocatechuic acid (PCA) is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon. The present study investigated the inhibitory mechanism of PCA on α-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo. Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of α-glucosidase. Driven by hydrogen bonds and van der Waals interactions, PCA reversibly bound with α-glucosidase to form a stable α-glucosidase-PCA complex in a spontaneous manner. The computational simulation found that PCA could insert into the active cavity of α-glucosidase and establish hydrogen bonds with catalytic amino acid residues. PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues. PCA also exhibited postprandial hypoglycemic capacity in diabetic mice. This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

Kinetics and molecular modeling studies on the inhibition mechanism of GH13 α-glycosidases by small molecule ligands

Alpha-glucosidase inhibitors play an important role in Diabetes Mellitus (DM) treatment since they prevent postprandial hyperglycemia. The Glycoside Hydrolase family 13 (GH13) is the major family of enzymes acting on substrates containing α-glucoside linkages, such as maltose and amylose/amylopectin chains in starch. Previously, our group identified glycoconjugate 1H-1,2,3-triazoles (GCTs) inhibiting two GH13 α-glycosidases: yeast maltase (MAL12) and porcine pancreatic amylase (PPA). Here, we combined kinetic studies and computational methods on nine GCTs to characterize their inhibitory mechanism. They all behaved as reversible inhibitors, and kinetic models encompassed noncompetitive and various mechanisms of mixed-type inhibition for both enzymes. Most potent inhibitors displayed Ki values of 30 μM for MAL12 (GPESB16) and 37 μM for PPA (GPESB15). Molecular dynamics and docking simulations indicated that on MAL12, GPESB15 and GPESB16 bind in a cavity adjacent to the active site, while on the PPA, GPESB15 was predicted to bind at the entrance of the catalytic site. Notably, despite its putative location within the active site, the binding of GPESB15 does not obstruct the substrate's access to the cleavage site. Our study contributes to paving the way for developing novel therapeutic strategies for managing DM-2 through GH13 α-glycosidases inhibition.

Development of an Improved Adenovirus Vector and Its Application to the Treatment of Lifestyle-Related Diseases.

The number of patients with lifestyle-related diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has continued to increase worldwide. Therefore, development of innovative therapeutic methods targeting lifestyle-related diseases is required. Gene therapy has attracted considerable attention as an advanced medical treatment. Safe and high-performance vectors are essential for the practical application of gene therapy. Replication-incompetent adenovirus (Ad) vectors are widely used in clinical gene therapy and basic research. Here, we developed a novel Ad vector, named Ad-E4-122aT, exhibiting higher and longer-term transgene expression and lower hepatotoxicity than conventional Ad vectors. We also elucidated the mechanisms underlying Ad vector-induced hepatotoxicity during the early phase using Ad-E4-122aT. Next, we examined the therapeutic effects of the genes of interest, namely zinc finger AN1-type domain 3 (ZFAND3), lipoprotein lipase (LPL), and lysophospholipid acyltransferase 10 (LPLAT10), on lifestyle-related diseases using Ad-E4-122aT. We showed that the overexpression of ZFAND3 in the liver improved glucose tolerance and insulin resistance. Liver-specific LPL overexpression suppressed hepatic lipid accumulation and improved glucose metabolism. LPLAT10 overexpression in the liver suppressed postprandial hyperglycemia by increasing glucose-stimulated insulin secretion. Furthermore, we also focused on foods to advance research on the pathophysiology and treatment of lifestyle-related diseases. Cranberry and calamondin, which are promising functional foods, attenuated the progression of MASLD/NAFLD. Our findings will aid the development of new therapeutic methods, including gene therapy, for lifestyle-related diseases such as T2DM and MASLD/NAFLD.

Basal Hyperglycemia Contributes More Than Fifty Percent to Time in Range in Pregnant Women with Type 1 Diabetes.

To evaluate the relative contribution of basal hyperglycemia (BHG) and postprandial hyperglycemia (PHG) to the time in range (TIR) categories and adverse pregnancy outcomes in pregnant women with type 1 diabetes mellitus (T1DM). This observational study included 112 pregnancies with T1DM from the CARNATION study who wore continuous glucose monitoring (CGM) devices during pregnancy. The data from CGM were analyzed for TIR (range, 3.5-7.8 mmol/L), areas under the curve (AUC) of PHG, AUC of BHG, basal and postprandial hyperglycemia contribution rates. The contribution rates of BHG and PHG to the different levels of TIR(＜60%, 60-78%, ≥78%) and adverse pregnancy outcomes were analyzed. The participants' average age was 28.8±3.9 years with a diabetes duration of 8.4±6.2 years. All women experienced a mean TIR of 75.6±19.0% and a mean HbA1c of 6.2±1.1% during pregnancy. The BHG contribution accounted for 74.9(36.8, 100)%, 69.2(13.4, 100)%, and 66.5(10.0, 100)% (P＜0.001) and PHG accounted for 25.1(0, 63.2)% and 30.8(0, 86.6)% and 33.5(0, 90.0)% (P＜0.001) when participants experienced the TIR＜60%, 60-78%, ≥78%, respectively. Participants with higher BHG contribution rates tended to have more adverse pregnancy outcomes. Basal hyperglycemia was the major contributor to TIR during pregnancy. Along with controlling the postprandial hyperglycemia, pregnant women with T1DM who did not reach the target of TIR may benefit more from the optimization of insulin regimens focusing on reducing basal glucose.

Functional assessments of Psidium guajava L. and Morus alba L. leaf extracts on postprandial glucose control

AbstractDiabetes is a leading cause of death, according to statistics published by the Department of Health, Executive Yuan of Taiwan. In modern medicine, diabetes can be controlled using various medications; however, some drugs often have undesirable side effects. It therefore became a goal to find plant‐based material that can reduce glucose concentration in the blood while reducing the incidence of complications and not causing side effects. Alpha‐glucosidase inhibitors (AGIs) are effective glucose‐lowering medicines and are enzymes essential to carbohydrate digestion. Inhibition of α‐glucosidase leads to a delayed and reduced rise in postprandial blood glucose levels. This study evaluates the inhibitory effect of mixed extracts of Psidium guajava L. and Morus alba L. leaves on α‐glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α‐glucosidase activity was assayed in vitro. Half maximal inhibitory concentration (IC50) values of Psidium guajava L. and Morus alba L. were 2.25 and 0.1 mg/mL, respectively. The IC50 value of a commercial anti‐hyperglycemic agent (Glucobay) is 6.41 mg/mL. The IC50 value of a mixture of extracts of Psidium guajava L. and Morus alba L. was 0.07 mg/mL. In cytotoxicity tests, survival percentages and shape did not significantly affect the murine embryonic liver cell line (BNL CL.2) when treated with varying concentrations of mixture extracts for varying periods of time. In summary, Psidium guajava L. and Morus alba L. showed positive anti‐diabetes activity and suggested promising potential for alternative functional foods for diabetes mellitus (DM) patients.

‘Retatruide’ drug trial: A paradigm shift in Type 2 Diabetes management

Type 2 diabetes mellitus (T2DM) is a chronic medical condition characterised by persistent hyperglycemia caused by insulin resistance and impaired beta cell function. Typically, it occurs in individuals aged 45 and above, but due to the growing prevalence of obesity and sedentary lifestyle, it is increasingly being diagnosed in younger adults and adolescents. A positive family history of T2DM and specific genes such as TCF7L2 and PPARG also play an essential role.[1] Consequently, persistent hyperglycemia in type 2 DM can give rise to a range of microvascular complications such as retinopathy, neuropathy and nephropathy and macrovascular complications such as coronary artery and cerebrovascular diseases. T2DM accounts for 90% of the cases of diabetes, raising concern among the healthcare sector worldwide. In 2017, approximately 462 million individuals were affected by type 2 DM, accounting for 6.28% of the world’s population. By 2030, it is estimated that the global prevalence will rise to 7079 individuals per 100,000.[2] To prevent the complications caused by T2DM, it is essential to prioritize glycemic control. First and foremost, effective dietary control is pivotal. It has been established that obesity in individuals with T2DM is closely associated with insulin resistance and defects in insulin secretions thus managing the calorie intake is mandatory. However, pharmacologic intervention with oral glucose-lowering agents or insulin therapy is necessary when the patient’s blood glucose doesn’t fall within normal limits despite weight reduction, exercise and dietary modifications. The first line pharmacological agent used is Metformin, an oral medication that reduces glucose production in the liver. Additionally, insulin secretagogues such as sulfonylureas and glinides promote insulin release by stimulating beta cells. Thiazolidinediones is another example of an oral agent used to treat diabetes by enhancing glucose uptake by the muscle, liver and adipose tissue.[3] Furthermore, it is crucial to understand that the Incretin effect, responsible for stimulating insulin secretion after meals, is primarily mediated by gut-derived incretin hormones known as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). However, patients with type 2 diabetes (T2DM) commonly exhibit defects in this process. To address this issue, in addition to oral medications, injectable drugs such as RA-GLP1 (Semaglutide, Dulaglutide) are administered to emulate the actions of human GLP-1 effectively. These injectable treatments are vital in reducing postprandial hyperglycemia and have become indispensable in managing T2DM. ---Continue

Probing benzenesulfonamide–thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II

Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities. Compounds 4d and 4e showed potent inhibitory activities (IC50 = 0.440 and 0.3456 μM), comparable with that of the positive control (acarbose; IC50 = 0.420 μM). All the synthesized derivatives were also tested for their inhibitory activities against hCA I, II, IX, and XII. They exhibited different levels of inhibition against these isoforms. Compound 4d outstood as the most potent one against hCA II with Ki equals to 7.0 nM, more potent than the reference standard (acetazolamide; Ki = 12.0 nM). In silico studies for the most active compounds within the active sites of α-glucosidase and hCA II revealed good binding modes that can explain their biological activities. MM-GBSA refinements and molecular dynamic simulations were performed on the top-ranking docking pose of the most potent compound 4d to confirm the formation of stable complex with both targets. Compound 4d was screened for its in vivo antihyperglycemic efficacy by using the oral glucose tolerance test. Compound 4d decreased blood glucose level to 217 mg/dl, better than the standard acarbose (234 mg/dl). Hence, this revealed its synergistic mode of action on post prandial hyperglycemia and hepatic gluconeogenesis. Thus, these benzenesulfonamide thiazolidinone hybrids could be considered as promising multi-target candidates for the treatment of type II diabetes mellitus.

Design, synthesis, molecular dynamic simulation, DFT analysis, computational pharmacology and decoding the antidiabetic molecular mechanism of sulphonamide-thiazolidin-4-one hybrids

In search of novel antidiabetic agents, the study was framed to hybridize and synthesize molecules based on scaffolds of benzenesulfonamide and thiazolidine-4-one, efficiently synthesized (6a-6h) and structurally characterized by FTIR, 1H NMR 13C NMR and HRMS spectroscopy. The antidiabetic activity was assessed based on α-amylase inhibition, glucose uptake assay and PPAR-γ transcription factor assay. Compound 6b (4-(2-((E)-5-((Z)-2-hydroxybenzylidene)-4-oxo-2-(phenylimino) thiazolidin-3-yl) ethyl) benzenesulfonamide) demonstrated promising activity toward α-amylase inhibition having IC50 value of 29.51±1.35 µg/ml. A glucose uptake assay was performed for compounds (6a-6h) to assess the capacity of glucose uptake. Among them, Compound 6b exhibits notable glucose uptake with 88.71% in the yeast cell line. To support the glucose uptake findings of compound 6b, expression of PPAR-γ transcription factor was measured of compound 6b as compared to pioglitazone. Furthermore, induced fit docking was carried out to predict the refined pose of synthesized compounds in the α-amylase binding pocket. MD simulation studies confirmed the stability of compound 6b in the α-amylase binding pocket. Molecules were geometrically optimized by DFT theory using B3LYP 6–31 G (d, p**) basis set, and electronic properties were studied. Network pharmacology analysis for compound 6b identified key pathways involved in T2DM and postprandial hyperglycemia like PI3K-Akt pathway, Type II diabetes mellitus pathway metabolic pathway, and digestion of dietary carbohydrates pathway. These findings provide better insights into further developing benzenesulfonamide-based thiazolidin-4-one hybrids as antidiabetic agents.

Exercise Prescription for Postprandial Glycemic Management.

The detrimental impacts of postprandial hyperglycemia on health are a critical concern, and exercise is recognized a pivotal tool in enhancing glycemic control after a meal. However, current exercise recommendations for managing postprandial glucose levels remain fairly broad and require deeper clarification. This review examines the existing literature aiming to offer a comprehensive guide for exercise prescription to optimize postprandial glycemic management. Specifically, it considers various exercise parameters (i.e., exercise timing, type, intensity, volume, pattern) for crafting exercise prescriptions. Findings predominantly indicate that moderate-intensity exercise initiated shortly after meals may substantially improve glucose response to a meal in healthy individuals and those with type 2 diabetes. Moreover, incorporating short activity breaks throughout the exercise session may provide additional benefits for reducing glucose response.

Depletion of TBC1D4 improves the metabolic exercise response by overcoming genetically induced peripheral insulin resistance.

The RabGTPase-activating protein (RabGAP) TBC1D4 (=AS160) represents a key component in the regulation of glucose transport into skeletal muscle and white adipose tissue (WAT) and is therefore crucial during the development of insulin resistance and type-2 diabetes. Increased daily activity has been shown to be associated with improved postprandial hyperglycemia in allele carriers of a loss-of-function variant in the human TBC1D4 gene. Using conventional Tbc1d4-deficient mice (D4KO) fed a high-fat diet (HFD), we show that already a moderate endurance exercise training leads to substantially improved glucose and insulin tolerance and enhanced expression levels of markers for mitochondrial activity and browning in WAT from D4KO animals. Importantly, in vivo and ex vivo analyses of glucose uptake revealed increased glucose clearance in interscapular brown adipose tissue (iBAT) and WAT from trained D4KO mice. Thus, chronic exercise is able to overcome the genetically induced insulin resistance caused by the Tbc1d4-depletion. Gene variants in TBC1D4 may be relevant in future precision medicine as determinants of exercise response.

Prandial Insulins: A Person-Centered Choice.

Postprandial hyperglycemia, or elevated blood glucose after meals, is associated with the development and progression of various diabetes-related complications. Prandial insulins are designed to replicate the natural insulin release after meals and are highly effective in managing post-meal glucose spikes. Currently, different types of prandial insulins are available such as human regular insulin, rapid-acting analogs, ultra-rapid-acting analogs, and inhaled insulins. Knowledge about diverse landscape of prandial insulin will optimize glycemic management. Human regular insulin, identical to insulin produced by the human pancreas, has a slower onset and extended duration, potentially leading to post-meal hyperglycemia and later hypoglycemia. In contrast, rapid-acting analogs, such as lispro, aspart, and glulisine, are new insulin types with amino acid modifications that enhance their subcutaneous absorption, resulting in a faster onset and shorter action duration. Ultra-rapid analogs, like faster aspart and ultra-rapid lispro, offer even shorter onset of action, providing better meal-time flexibility. The Technosphere insulin offers an inhaled route for prandial insulin delivery. The prandial insulins can be incorporated into basal-bolus, basal plus, or prandial-only regimens or delivered through insulin pumps. Human regular insulin, aspart, lispro, and faster aspart are recommended for management of hyperglycemia during pregnancy. Ongoing research is focused on refining prandial insulin replacement and exploring newer delivery methods. The article provides a comprehensive overview of various prandial insulin options and their clinical applications in the management of diabetes.

Real-World Assessment of Personalized Approach With Voglibose Fixed-Dose Combination in Type 2 Diabetes Mellitus.

Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy. This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.). Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m2. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period. Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.

A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals.

We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating glycogen use would increase the disposal of the ingested glucose (i.e., OGTT; 75 g of glucose). Separated by at least 1 week, nine young-healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58±5% VO2MAX either in a thermoneutral (21±1ºC; NEUTRAL) or in a hot environment (33±1ºC; HEAT) eliciting similar energy expenditure (503±101 kcals). These two trials were compared to a no-exercise trial (NO EXER). Twenty min after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U- 13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149±35 vs 124±31 µmol·kg-1·min-1, p=0.010). However, during the following OGTT glucose Rd was similar in HEAT and NEUTRAL (i.e., 25.1±3.6 vs 25.2±5.3 µmol·kg-1·min-1, p=0.981). Insulin sensitivity (i.e., ISIMATSUDA) only improved in NEUTRAL compared to NO EXER (10.1±4.6 vs 8.8±3.7 a.u.; p=0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.

Study on Antidiabetic Potential of Sessuvium Portulacastrum Aqueous Extract: An In-Silico and In-Vitro Analysis

ABSTRACT Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.

Edible prodelphinidins that improve postprandial hyperglycemia were first discovered in Chinese bayberry ( Myrica rubra Sieb. et Zucc.) fruits

Edible prodelphinidins that improve postprandial hyperglycemia were first discovered in Chinese bayberry ( <em>Myrica rubra</em> Sieb. et Zucc.) fruits

Investigating the effect of polyphenols from nuts on human carbohydrate digestion in vitro

Recent studies have documented the importance of postprandial hyperglycaemia in the incidence of chronic diseases, including type 2 diabetes. Inhibition of digestive enzymes, including membrane-bound brush-border α-glucosidases, leads to slowed carbohydrate digestion and absorption, and reduced postprandial glycemia. Nuts are widely eaten around the world and have the potential to inhibit α-glucosidases through their content of polyphenols and other bioactive compounds. According to our recent systematic review(1), no study has investigated the inhibitory effects of nut extracts on human α-glucosidase activities. Almost all studies in this area have been conducted on yeast α-glucosidase, with only a few using rat α-glucosidase. While there is no sequence homology between yeast and human α-glucosidase, there is 74% to 78% sequence homology between rat and human α-glucosidases(1). The lack of studies on the effect of bioactive compounds from nuts on human α-glucosidases, along with the growing attention to nuts as an important component of a healthy diet with the potential to reduce the risk of chronic diseases(2), highlights the need for research to evaluate the inhibitory effect of nut extracts on human α-glucosidases. The aim of the current study is to explore the inhibitory effect of extracts from nuts on human carbohydrate digestive enzymes. Walnuts and almonds were ground and defatted with hexane, extracted in 80% (v/v) acetone, and further purified using solid-phase extraction to obtain phenolic-rich extracts. The Folin–Ciocalteu assay was used to approximate the polyphenol content of the samples. Following our recently published detailed protocol(3), cell-free extracts from human intestinal Caco-2/TC7 cells were used as a source of α-glucosidase in enzyme inhibition assays, with sucrose, maltose and isomaltose as substrates and appropriate controls. The assay products were quantified using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Glucose production in the presence of various concentrations of phenol-rich nut extracts was compared using a one-way ANOVA and half-maximal inhibitory concentration (IC50) values were calculated. The Folin–Ciocalteu data demonstrate that walnut extracts comprise a relatively high polyphenol content, with 18.1 ± 0.23 mg (epigallocatechin gallate [EGCG] equivalent) per gram of fresh weight, while almond extracts contain 0.87 ± 0.03 mg EGCG equivalent/g of fresh weight. The walnut phenolic-rich extract dose-dependently inhibited human intestinal sucrase and maltase activities (both p&lt;0.01), with IC50 values of 1.67 mg/mL and 2.84 mg/mL, respectively. We demonstrate that phenolic-rich walnut extracts can inhibit human α-glucosidases in vitro and therefore walnuts may contribute to slowing carbohydrate digestion in humans. As such, we plan to assess the effects of walnuts on postprandial glycaemia in vivo.

Understanding Antidiabetic Potential of Oligosaccharides from Red Alga Dulse Devaleraea inkyuleei Xylan by Investigating α-Amylase and α-Glucosidase Inhibition.

In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan were analysed as a potential mechanism to control postprandial hyperglycaemia for type-2 diabetes prevention and treatment. Xylan was purified from red alga dulse powder and used for enzymatic hydrolysis using Sucrase X to produce XOSs. Fractionation of XOSs produced xylobiose (X2), β-(1→3)-xylosyl xylobiose (DX3), xylotriose (X3), β-(1→3)-xylosyl-xylotriose (DX4), and a dulse XOS mixture with n ≥ 4 xylose units (DXM). The different fractions exhibited moderate MGAM (IC50 = 11.41-23.44 mg/mL) and α-amylase (IC50 = 18.07-53.04 mg/mL) inhibitory activity, which was lower than that of acarbose. Kinetics studies revealed that XOSs bound to the active site of carbohydrate digestive enzymes, limiting access to the substrate by competitive inhibition. A molecular docking analysis of XOSs with MGAM and α-amylase clearly showed moderate strength of interactions, both hydrogen bonds and non-bonded contacts, at the active site of the enzymes. Overall, XOSs from dulse could prevent postprandial hyperglycaemia as functional food by a usual and continuous consumption.

Inhibitory Activities of Thai Culinary Vegetables against Key Enzymes Relevant to Diabetes Mellitus and the Kinetics of Enzyme Inhibitions

Diabetes mellitus (DM) is one of the most challenging noncommunicable diseases, as it causes significant costs for medical treatment as well as high morbidity and mortality rates. Dietary plants with antidiabetic properties have been explored as an alternative to synthetic medicines to treat DM because of their safety and nutrition. Hence, the objective of the present study was to determine the inhibitory activities of twenty commonly consumed Thai culinary vegetables against α-glucosidase and α-amylase. All vegetables were extracted using deionized water, ethanol, and hexane at 150 rpm and 30°C for 24 hours. The enzyme inhibitory activities were performed using a colorimetric assay. Diverse results for α-glucosidase and α-amylase inhibitory activities were found for all vegetable extracts. The most potent anti-α-glucosidase activity was obtained from the ethanolic extract of Leucaena leucocephala (Lamk.) de Wit with the half maximal inhibitory concentration (IC50) of 13.39 ± 0.14 μg/mL, followed by the aqueous and ethanolic extracts of Polygonum odoratum Lour with IC50 of 25.60 ± 0.42 and 49.03 ± 0.72 μg/mL, respectively. All the samples exhibited mixed, noncompetitive, and uncompetitive inhibition. It can be concluded that the α-glucosidase and α-amylose inhibitory effects of the investigated extracts may be an indicator of antidiabetic potency, and these extracts might potentially be beneficial as functional components for postprandial hyperglycemia treatment.

Unlocking potential diabetes therapeutics: Insights into alpha-glucosidase inhibition

Diabetes mellitus (DM) stands as a significant global health challenge, ranking third among causes of mortality worldwide. Despite extensive endeavors, effective treatments for diabetes remain elusive. Alpha-glucosidase, a pivotal enzyme in glycoprotein metabolism regulation, emerges as a promising therapeutic target for mitigating postprandial hyperglycemia, a hallmark of diabetes. In this study, we employed advanced computational methodologies to identify inhibitors of lysosomal α-glucosidase. Leveraging pharmacophore-based virtual screening of a vast library of drug-like molecules, we unearthed 161 potential inhibitors capable of binding within the enzyme's active pocket. Subsequent molecular docking simulations yielded five lead molecules exhibiting robust binding affinities and favorable interaction profiles with critical catalytic residues. Further analysis through molecular dynamics simulations provided crucial insights into the stability and conformational dynamics of the inhibitor-enzyme complexes. Notably, certain residues emerged as pivotal for the retention of inhibitors within the active site. Our findings underscore the potential of LIG1-LIG5 as promising inhibitors against lysosomal α-glucosidase, presenting novel avenues for the development of effective diabetes therapeutics. This research enriches our understanding of the molecular underpinnings of diabetes treatment, facilitating targeted drug development strategies in the quest for improved patient outcomes.

Formulation and assessment of chickpea pulao using fenugreek seeds and Indian rennet to improve blood glycemic levels

AbstractDiabetes is becoming a significant health concern in Asia, where the prevalence has reached alarming levels. An important contributing factor is the consumption of high‐carbohydrate foods, including rice, bread, etc. These high‐carbohydrate foods pose a major risk to public health due to their impact on postprandial hyperglycemia. This research aimed to formulate a chickpea pulao (cooked Indian–Pakistani rice dish) and to evaluate its effects on postprandial blood glucose levels in type 2 diabetic individuals. Antioxidant potential and total phenolic contents of herbs at different concentrations (1, 3, 5, 7, and 9%) were measured through DPPH and Folin Ciocalteu assays. The antidiabetic potential was tested by α‐amylase and α‐glucosidase inhibition assays. After sensory evaluation, the best‐chosen concentration was used to formulate the chickpea pulao. The study trial was advertised under “DP trial,” and 12 participants were recruited. A single‐blind randomized cross‐over trial was conducted for 3 weeks with a one‐week wash‐over time in between. Participants' preprandial and postprandial blood glucose levels were recorded for control and intervention recipes. Results indicated that both fenugreek seeds (FS) and Indian rennet (IR) showed good antioxidant and hypoglycemic activity (p = .000) in raw and boiled extracts. For DPPH, the IC50 values of unboiled and boiled combined (FS + IR) extracts were calculated as 7.4% and 8.02%, respectively. Similarly, for α‐amylase, the IC50 values of combined IR and FS unboiled and boiled extracts were 6.58% and 6.83%, and for α‐glucosidase inhibition assay, the values were measured as 14.98% and 16.24%. The single‐blind randomized cross‐over trial showed that consuming the intervention recipe significantly reduced postprandial hyperglycemia (p = .000) in type 2 diabetic participants. The intervention recipe decreased hyperglycemia by approximately 15% daily compared to the control recipe. Incorporation of hypoglycemic herbs into dietary patterns can work as an adjunct therapy for diabetes management, especially in populations with a high prevalence of this disease.