Dipeptidyl Peptidase-4 Inhibitors Research Articles

Dipeptidyl peptidase-4 inhibitors may lower body temperature: A case-control study

AimsDipeptidyl peptidase-4 inhibitors (DPP4i) enhance GABAergic transmission via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor pathway. Oral γ-aminobutyric acid (GABA) administration reduces body temperature in humans; thus, DPP4i may reduce body temperature in humans. Therefore, this study aimed to determine the effects of DPP4i administration on the body temperature of patients with type 2 diabetes (T2D). MethodsThis study included 128 outpatients with T2D who visited the hospital monthly from May to July 2022. The DPP4i group included 64 patients treated with DPP4i while the non-DPP4i group included 64 patients not treated with DPP4i. Body temperature was measured at the axilla point upon entry to the hospital and was compared between the two groups. ResultsThe means of age, body mass index, T2D duration, systolic blood pressure, diastolic blood pressure, serum creatinine level, casual triglyceride level, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, casual plasma glucose level, and glycated hemoglobin level were not significantly different between the two groups. The mean body temperatures (°C) were 36.1 ± 0.2 and 36.4 ± 0.17 in the DPP4i and non-DPP4i groups, respectively (p = 1.123 E−05). ConclusionsDPP4i reduced the body temperature of patients with T2D.

Effect of Dipeptidyl Peptidase-4 Inhibitors Supplementation on Non-Alcoholic Steatohepatitis in Adolescents with Type 1 Diabetes Mellitus

Abstract Background Many patients with type 1 diabetes mellitus (T1DM) had histological evidence of steatosis and met the histological criteria for non-alcoholic steatohepatitis (NASH). Accumulating data suggested that dipeptidyl peptidase-4 (DDP-4) enzyme is involved in the development of various chronic liver diseases. Some studies showed the beneficial effect of DDP-4 inhibitors in liver injury for their ability in modulating fatty acid oxidation, decreasing lipogenesis and improving hepatic glucose metabolism. Objectives Therefore, we performed a randomized-controlled trial to assess the effect of the oral DPP- 4 inhibitor vildagliptin as an add-on therapy on NASH in adolescents with T1DM as well as its effect on glycemic control, lipid profile. Methods This study included 60 adolescents with T1DM and NASH. Patients were randomly assigned into two groups; intervention group who received oral vildagliptin (50 mg daily). The other group did not receive any supplementation and served as a control group. Both groups were followed- up for six months with assessment of fasting and 2 hours post-prandial blood glucose levels, HbA1c, liver function tests, fasting lipid profile and hepatic steatosis index. Results Supplementation with oral DPP-4 inhibitor vildagliptin was safe and well-tolerated. After six months, Vildagliptin adjuvant therapy for the intervention group resulted in a significant decrease of systolic and diastolic blood pressure as well as insulin dose (p < 0.001). Blood glucose levels, HbA1c, liver enzymes, triglycerides, total cholesterol and hepatic steatosis index were significantly lower after vildagliptin therapy compared with baseline levels and compared with the control group (p < 0.001). Conclusions The DDP-4 inhibitor vildagliptin in a once daily dose of 50 mg orally for six months as an add-on therapy for adolescents with T1DM and NASH was safe and improved glycemic control and dyslipidemia while decreasing steatosis; hence, preventing disease progression.

DPP4 Inhibitors and Hypersensitivity Reactions: Experiences From Clinical Pharmacology and Diabetes and Allergy-Asthma Therapeutics Specialty Clinics

DPP4 Inhibitors and Hypersensitivity Reactions: Experiences From Clinical Pharmacology and Diabetes and Allergy-Asthma Therapeutics Specialty Clinics

Use of a PK/PD Model to Select Cetagliptin Dosages for Patients with Type 2 Diabetes in Phase 3 Trials.

Cetagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of patients with type 2 diabetes (T2D). Several phase 1 studies have been conducted in China. Modelling and simulation were used to obtain cetagliptin dose for phase 3 trials in T2D patients. A pharmacokinetic (PK)/pharmacodynamic (PD) model and model-based analysis of the relationship between hemoglobin A1c (HbA1c) and dosage was explored to guide dose selection of cetagliptin for phase 3 trials. The PK/PD data were derived from four phase 1 clinical studies, and sitagliptin 100 mg was employed as a positive control in studies 1, 3, and 4. The PK profiles of cetagliptin were well described by a two-compartment model with first-order absorption, saturated efflux, and first-order elimination. The final PD model was a sigmoid maximum inhibitory efficacy (Emax) model with the Hill coefficient. The final model accurately captured cetagliptin PK/PD, demonstrated by goodness-of-fit plots. Based on weighted average inhibition (WAI), the relationship between HbA1c and dose was well displayed. Cetagliptin 50 mg once daily or above as monotherapy or as add-on therapy appeared more effective in HbA1c reduction than sitagliptin 100 mg. Cetagliptin 50 mg or 100 mg once daily was selected as the dose for phase 3 trials of cetagliptin in T2D patients. The PK/PD model supports dose selection of cetagliptin for phase 3 trials. A model‑informed approach can be used to replace a dose-finding trial and accelerate cetagliptin's development.

New labdane diterpenoids from Alpinia galanga: A new type of GLP-1 secretagogues targeting the PKA-CREB and PI3K-Akt signaling axes.

Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.0%-413.8% at 50 µM. A mechanistic study manifested that the most effective compound 12 upregulated the mRNA expression of Gcg and Pcsk1, and the protein phosphorylation of PKA, CREB, and GSK3β, but was inactive on GPBAR and GPR119 receptors. Network pharmacology analysis indicated that the PI3K-Akt pathway was involved in the GLP-1 stimulation of 12, which was highly associated with AKT1, CASP3, PPARG, and ICAM1 proteins. This study suggests that A. galanga is rich in diverse labdane diterpenoids with GLP-1 promoting effects, representing a new type of antidiabetic candidates from natural sources.

Elucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss-Newton method.

The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM). The CGNM facilitated the exploration of parameters in rat and human PBPK models for LNG and the determination of parameter identifiability. Through PBPK-CGNM analysis using reported autoradiography data ([14C]-LNG) in wild-type and Dpp-4-deficient rats, DPP-4-specific distributions of LNG in various tissues were clearly differentiated from nonspecific parts. By fitting to human plasma concentrations and urinary and fecal excretions of LNG after intravenous and oral administrations, multiple unknown PBPK parameters were simultaneously estimated by the CGNM. Notably, the amount of tDPP-4 and the reabsorption clearance for LNG-DPP-4 complexes were identifiable, indicating their critical role in explaining the complex nonlinear pharmacokinetics of LNG. Compared with previous PBPK analyses, the CGNM allowed us to incorporate greater model complexity (e.g., consideration of tDPP-4 expressions and invitro binding kinetics), ultimately resulting in a more accurate reproduction of LNG's TMDD. In conclusion, by considering LNG as a high-affinity probe for DPP-4, comprehensive PBPK-CGNM analyses suggested a dynamic whole-body distribution of DPP-4, including its involvement in the renal reabsorption of LNG.

Optimization of ultrasound-assisted extraction method of Syzygium cumini leaves based on extraction yield, content of bioactive compound, and inhibition of dipeptidyl peptidase IV enzyme activity using response surface methodology

Syzygium cumini leaves show potential to be developed as herbal medicine products against diabetes mellitus due to their high polyphenol contents. S. cumini was optimized using response surface methodology and Box–Behnken design with solvent solid ratio, solvent concentration, time and temperature, extraction yield, total flavonoid content (TFC), total phenolic content (TPC), and dipeptidyl peptidase IV (DPP-IV) enzyme inhibitory activity to obtain an effective and optimal extraction method. The conditions were achieved using a 70% ethanol solvent for the extraction, with a solvent–solid ratio of 21 v/w and run at 20°C for 30 min. The results showed an extraction yield of 83.875%, with TFCs measuring at 3.068 mg QE/g, TPCs of 65.029 mg GAE/g, and DPP-IV enzyme inhibition activity of 66.079%. Further analysis of the phytochemical profile using untargeted liquid chromatography-high-resolution mass spectrometry showed the presence of amine, amide, and fatty acid derivatives as major constituents. In addition, major flavonoids observed were myricetin and myricitrin, accounting for 0.2%. Ursolic acid and 25-azacholesterol accounted for 1.03% of the phenolics detected.

Review on the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway in diabetes: mechanistic insights and therapeutic implications.

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1β and interleukin-18, driving insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. These processes contribute to diabetic complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases (CVD). Here we discuss the various transcriptional, epigenetic, and gut microbiome mediated regulation of NLRP3 activation in diabetes. Different classes of oral hypoglycemic drugs modulate NLRP3 inflammasome activity through various mechanisms: sulfonylureas inhibit NLRP3 activation and reduce inflammatory cytokine levels; sodium-glucose co-transporter 2 inhibitors (SGLT2i) suppress inflammasome activity by reducing oxidative stress and modulating intracellular signaling pathways; dipeptidyl peptidase-4 inhibitors mitigate inflammasome activation, protecting against renal and vascular complications; glucagon-like peptide-1 receptor agonists attenuate NLRP3 activity, reducing inflammation and improving metabolic outcomes; alpha-glucosidase inhibitors and thiazolidinediones exhibit anti-inflammatory properties by directly inhibiting NLRP3 activation. Agents that specifically target NLRP3 and inhibit their activation have been identified recently such as MCC950, Anakinra, CY-09, and many more. Targeting the NLRP3 inflammasome, thus, presents a promising strategy for managing diabetes and its complications, with oral hypoglycemic drugs offering dual benefits of glycemic control and inflammation reduction. Further research into the specific mechanisms and long-term effects of these drugs on NLRP3 inflammasome activity is warranted.

Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data.

Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients' quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan. This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups. The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75-0.92, P = 0.0003). In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM. Graphical abstract available for this article.

Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220–280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

SITAGLIPTIN AMELIORATES ATORVASTATIN INDUCED HEPATOTOXICITY IN RATS

Atorvastatin (ATOR) is the most widely used statin for the treatment of hypercholesterolemia, which is the most common cause of severe liver injury. Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor (DPP4-I) used clinically as oral anti-diabetic agent. This study aimed to identify the effect of sitagliptin (SITA) pretreatment against Atorvastatin (ATOR) induced hepatotoxicity in albino rats. Twenty-five rats were divided into five groups (5 rats in each); normal control, ATOR, SITA and two sitagliptin groups, which pretreated with sitagliptin 10 and 20 mg/kg/day in combination with ATOR 20mg /kg / day for eight consecutive days prior to ATOR. The results revealed that ATOR induced noticeable hepatic injury in the form of moderate Hepatoportal + sinusoidal congestion, all Zonal changes, moderate Cloudy swelling + hydropic degeneration, moderate Fatty change and mild Apoptosis. Biochemical analysis exposed a significant rise in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in ATOR group. Increased Proinflammatory TNF-alpha, Oxidative stress MDA and depressed antioxidant system of GSH were evident in ATOR group. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological changes induced by ATOR. In conclusion, sitagliptin ameliorated the hepatotoxicity induced by atorvastatin. This effect was probably based through suppression of inflammatory, oxidative stress and apoptotic processes. Sitagliptin might exert beneficial effect on diabetic hepatic disorders which mandate further clinical research.

Precooked Jack Bean [Canavalia ensiformis (L.) DC] Sprout: Generation of Dipeptidyl Peptidase-IV Inhibitory Peptides during Simulated Digestion.

Bioactive peptides generated from jack bean sprouts are reported to function as dipeptidyl peptidase IV (DPP-IV) inhibitors. However, no studies have investigated the effect of precooking followed by simulated digestion using pepsin-pancreatin to increase DPP-IV inhibitory peptide generation in jack bean sprouts. Therefore, the present study aimed to explore the generation of DPP-IV inhibitory peptides from precooked jack bean [Canavalia ensiformis (L.) DC] sprouts during simulated digestion with pepsin-pancreatin. The results showed that peptide fractions of the sample hydrolysate with molecular weight <1 kDa exhibited the strongest DPP-IV inhibitory activity (84.77%±0.49%) after simulated digestion. This activity was slightly greater than that (74.12%±0.85%) observed prior to simulated digestion. These findings demonstrate that the DPP-IV inhibitory activity of precooked jack bean sprouts can be retained following simulated digestion. Moreover, our investigation revealed the sequences of two novel peptides following simulated digestion with critical amino acids. The presence of alanine and glycine at the penultimate N-terminus of AAGPKP and LGDLLK confirmed the presence of DPP-IV inhibitors. Both peptide sequences are nontoxic and interact with the catalytic sites of enzymes through hydrogen bonds.

Molecular Docking and ADMET Profiling of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin from Dalbergia sissoo: In Silico Prediction in Antidiabetic Potential

Molecular Docking and ADMET Profiling of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin from Dalbergia sissoo: In Silico Prediction in Antidiabetic Potential

Novel Bioactive Peptides from Red Bigeye (Priacanthus macracanthus) Flesh Protein

Red bigeye (Priacanthus macracanthus) is a common fish species in Malaysia. This study reported an in silico assessment of the main proteins in red bigeye flesh as precursors for bioactive peptides. Six major proteins were chosen as precursors from the proteomic profiles of red bigeye proteins. Analyses using the BIOPEP-UWM database found that Protein number 4 gave the highest total number of bioactive peptides (5052 peptides), with dominant bioactivity in angiotensin-I-converting enzyme (ACE) inhibition (1571 peptides) and dipeptidyl peptidase-IV (DPP-IV) inhibition (2238 peptides). The ACE inhibitors had a frequency of bioactive fragment occurrences (A) of 0.4098, while the DPP-IV inhibitors gave a frequency of 0.5805. In silico proteolysis using BIOPEP-UWM found that pepsin (pH &gt; 2) was the most promising proteinase in releasing a high number of DPP-IV and ACE inhibitory peptides. A novel peptide with significant potential was identified as QYKF. This study shows that red bigeye is a potential source of antihypertensive and antidiabetic peptides.

Dipeptidyl peptidase 4: A predictor of ferroptosis in ulcerative colitis.

With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied. The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package "CancerSubtype" and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe2+ with commercial FerroOrange kits. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-β, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression. DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC.

Perioperative Management Of Diabetes Mellitus In Older Hip Fracture Patients

Abstract Background Hip fracture is one of the most serious injuries sustained by older adults worldwide, associated with increased morbidity and almost 25% mortality at one year. Pre-existing comorbidity worsens prognosis, e.g. hip fracture patients with Diabetes Mellitus (DM) have increased mortality rates, worse functional outcomes, and higher post-operative complications rates. Perioperative blood glucose optimisation may improve outcomes, however this can be challenging due to periods of fasting and reduced intake, as well as complications such as infection. Local guidelines for the peri-operative management of DM have been developed and are sign-posted in our hip fracture integrated admission document. This audit aimed to compare current practice with those recommended in local guidance. Methods Since 1st January 2024, 31 hip fracture patients aged ≥65 years with DM have been admitted. Charts were available on twenty patients, and hence reviewed. Results Of 20 patients, four were on insulin; 13 on metformin; four on sulphonylureas; five on SGLT2 inhibitors; and six on DPP4 inhibitors. No intraoperative hypoglycemic events nor episodes of Diabetic Ketoacidosis were documented; however, ketones were not checked in the majority of patients during admission. Eleven (55%) had HbA1C either done in the previous six months or during admission. Blood Sugar Levels were checked on admission in 9/20 (45%). The protocol was followed in only one patient on insulin; and 5/13 metformin patients. The protocol was followed in all Sulphonylurea prescriptions, and in 4/5 SGLT2 inhibitor prescriptions, however these medications were not held by the Orthopaedic team, rather by nursing staff while the patient was fasting pre-operatively. Conclusion This audit demonstrates poor adherence to local guidance on peri-operative management of diabetes, particularly perioperative insulin adjustments. We aim to develop an educational intervention (including group teaching, plus distribution of flashcards and posters) for Orthopaedic SHOs and interns and re-audit in the coming months.

Glucose-lowering drugs and liver-related outcomes among individuals with type 2 diabetes: A systematic review of longitudinal population-based studies.

While randomized controlled trials data on the long-term effect of glucose-lowering drugs (GLDs) on liver-related outcomes are lacking, population-based studies have evaluated the associations of GLDs with liver-related outcomes in individuals with type 2 diabetes (T2D). we aimed to conduct a systematic review of population-based studies evaluating the effects of GLDs on liver-related outcomes in people with T2D. PubMed, Web of Science, and Embase databases were systematically searched for population-based studies testing the associations of GLDs with liver-related outcomes in individuals with T2D and no liver disease other than non-alcoholic fatty liver disease (NAFLD) from inception to 23 February 2024. GLDs included SGLT2is, TZDs, insulin, GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP4Is). Ten cohort studies, comprising 1,274,641 participants, met the inclusion criteria. The median follow-up period ranged from 8.9 to 76 months. Of all the GLDs under investigation, SGLT2is were associated with the strongest reduction in NAFLD incidence, cirrhosis, and composite liver-related events compared to other medications. TZDs were associated with a reduced risk of developing NAFLD and cirrhosis but were not significantly associated with a lower incidence of hepatocellular carcinoma. GLP-1 RAs demonstrated a significant association with reduced liver-related mortality. Observational data from population-based studies suggest that GLDs such as SGLT2is are associated with beneficial long-term liver-related outcomes in T2D patients with NAFLD. Additional studies, including randomized controlled trials with long-term follow-up, are needed to confirm these findings. PROSPERO CRD442024536872.

Bioactive Peptides from Corn (Zea mays L.) with the Potential to Decrease the Risk of Developing Non-Communicable Chronic Diseases: In Silico Evaluation.

Studies have shown that corn (Zea mays L.) proteins, mainly α-zein, have the potential to act on therapeutic targets related to non-communicable chronic diseases, such as high blood pressure and type 2 diabetes. Enzymatic hydrolysis of proteins present in foods can result in a great diversity of peptides with different structures and possible bioactivities. A review of recent scientific research papers was performed to show evidence of the bioactive properties of corn peptides by in vitro assays. The α-zein amino acid sequences were identified in the UniProtKB protein database and then analyzed in the BIOPEP database to simulate enzymatic digestion and verify the potential biological action of the resulting peptides. The peptides found in the BIOPEP database were categorized according to the probability of presenting biological action using the PeptideRanker database. The aim was to use existing data to identify in silico the potential for obtaining biologically active peptides from α-zein, the main storage protein of corn. The analysis showed that the majority of peptide fragments were related to the inhibition of angiotensin-converting enzyme, followed by the inhibition of dipeptidyl peptidase IV and dipeptidyl peptidase III. Many drugs used to treat high blood pressure and type 2 diabetes work by inhibiting these enzymes, suggesting that corn peptides could be potential alternative agents. In vitro studies found that the primary bioactivity observed was antioxidative action. Both in vitro and in silico approaches are valuable for evaluating the bioactive properties resulting from protein hydrolysis, such as those found in α-zein. However, conducting in vitro studies based on prior in silico evaluation can be more efficient and cost-effective.

Exploring the Potential of Moringa Oleifera Phytochemicals as Inhibitors of Dipeptidyl Peptidase-4 (DPP-4) in Diabetes Mellitus: A Molecular Docking Approach

Abstract Diabetes mellitus (DM) is a global health concern characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. Type 2 diabetes (T2DM), the most prevalent form, is largely driven by obesity and a sedentary lifestyle, contributing to over 95% of diabetes cases worldwide. The current treatment regimens for T2DM, including Dipeptidyl Peptidase-4 (DPP-4) inhibitors, aim to enhance insulin secretion but are often associated with adverse side effects. This has intensified the search for natural, safer alternatives with comparable efficacy. Moringa oleifera, a highly valued plant with an extensive history in traditional medicine, has shown promising antidiabetic properties. This research explores the potential of Moringa oleifera-derived phytochemicals as natural DPP-4 inhibitors using in-silico molecular docking techniques. The study identifies and evaluates the binding affinities of these phytochemicals to the DPP-4 enzyme, aiming to predict their inhibitory potential and minimal side effects, thereby contributing to the development of novel, safer hypoglycemic drugs. The results indicate the compounds’ potential as effective DPP-4 inhibitors with promising hypoglycemic properties. Specifically, piceatannol exhibited the highest binding affinity of -7.9 kcal/mol, whereas vanillic acid had the lowest at -5.7 kcal/mol. This study underscores the potential of Moringa oleifera as a natural, safer alternative in the development of novel anti-diabetic drugs, contributing to the growing body of research on plant-based therapeutics for diabetes management.

Comparative Study of Hypovitaminosis B12 Associated with Metformin in Combination with Sulfonylurea or Dpp-4 Inhibitors

Comparative Study of Hypovitaminosis B12 Associated with Metformin in Combination with Sulfonylurea or Dpp-4 Inhibitors