Treatment Of Diabetes Mellitus Research Articles

Investigating predictive factors in treatment response with metformin in patients with gestational diabetes mellitus: a cross-sectional analytical-descriptive study.

As the utilization of metformin for gestational diabetes mellitus (GDM) treatment continues to rise, a substantial segment of these patients will ultimately necessitate insulin during their therapeutic journey. Hence, assessing patients' clinical and laboratory attributes becomes invaluable in determining their likelihood of responding favorably to metformin medication. This discernment aids in selecting an optimal management approach, wherein the patients most likely to benefit significantly from metformin are identified, while alternative therapies like insulin are considered for individuals with a lower probability of treatment response. This was a cross-sectional analytical-descriptive study of individuals with GDM. Initially, the subject's laboratory results and demographic information were submitted. Following that, metformin was administered to all subjects along with counseling on maintaining a healthy diet and lifestyle. Following a 4-week interval, the patients were reassessed and divided into two groups based on their response to metformin medication and then analyzed. 807 people participated in this study, of which 329 people (40.8%) responded to treatment and the failure rate of metformin treatment was 59.2%. This research revealed that the predictive factors of response to metformin medication were, respectively, the amount of 1-hour oral glucose tolerance test (OGTT) (OR = 62.66), 2-hour postprandial plasma glucose (OR = 54.04), 2-hour OGTT (OR = 17.37), followed by the history of abortion (OR = 14.88), the number of pregnancies (gravida 3 and more) (OR = 5.06) and history of infertility (OR = 2.6). The current study's findings indicated that to enhance GDM care, metformin prescriptions should be prescribed to patients depending on their clinical characteristics and laboratory results.

Prevalence of obesity, determinants, and its association with hyperglycaemia among community dwelling older adolescents in India.

Globally, obesity and diabetes mellitus (DM) are emergent public health concerns in the adolescent population. India, home to the largest adolescent population and the second largest diabetes cohort is experiencing rapid but unplanned urbanization, with accompanying unhealthy nutritional transition, and sedentary lifestyle. To determine prevalence and determinants of obesity and hyperglycaemia and their association among community-dwelling older adolescents (15-19 years) in India. This cross-sectional analysis from the national family health survey-5 included data of 258028 adolescents aged 15-19 across India (2019-2021). The survey employed stratified two-stage sampling, with systematic random sampling in rural and urban areas. Statistical analysis included descriptive statistics, bivariate, and multivariable logistic regression, employing generalized linear models. The weighted prevalence of DM was 1.09% including 0.77% [95% confidence interval (CI): 0.72-0.83] previously diagnosed and 0.32% (95%CI: 0.29-0.35) newly diagnosed cases detected on survey screening. On adjusted analysis, increasing age, higher education levels, higher wealth index, and overweight/obesity were the factors significantly associated with presence of DM. Only 61% of the adolescents with previously diagnosed DM were on anti-diabetes treatment. The weighted prevalence of overweight/obesity among older adolescents was 6.9% with significantly higher odds in the male sex, having higher educational levels, urban residence, and those with a higher wealth index. Nearly one in hundred older adolescents in India have diabetes, with one in three undiagnosed. Strengthening DM screening and treatment access among adolescents through public health programs is urgently warranted.

Activity Test of The Combination Papaya Leaf Extract (Carica papaya L.) and Soursop Leaf Extract (Annona mu-ricata L.) on Decreasing Blood Glucose Levels in Rats (Rattus norvegicus)

Diabetes mellitus (DM) is one of the most common health disorders and its prevalence rate is increasing every year. Natural compounds can be an alternative treatment for DM. Previous re-search reports for papaya leaves (Carica papaya L.) and soursop leaves (Annona muricata L.) showed activity in lowering blood glucose levels when used alone. Therefore, in this study, the two samples were combined to lower blood glucose levels. Both leaves were extracted using the decoction method. This study aims to identify secondary metabolite compounds in papaya leaf extract (Carica papaya L.) and soursop leaf extract (Annona muricata L.), then continued with determining the activity and effectiveness of lowering blood glucose levels. The results of the identification of secondary metabolite compounds showed several groups of compounds such as flavonoids, saponins and tannins. The combination of papaya leaf extract and soursop leaf extract showed a decrease in blood glucose levels. In more detail, EDPS 1:2 and EDPS 2:1 were statistically significant against negative controls. EDPS 1:2 showed the most effective percentage reduction in blood glucose levels at 22.72%

TRATAMENTO DE DIABETES MELLITUS TIPO II POR MEIO DA MUDANÇA DO ESTILO DE VIDA – RELATO DE CASO.

Type II diabetes mellitus is a chronic non-communicable disease characterized by hyperglycemia due to pancreatic dysfunction and/or insulin resistance, leading to tissue damage and long-term complications. Currently, the medical literature supports non-pharmacological and pharmacological treatments for managing the disease, with the goal of achieving the therapeutic target of glycated hemoglobin with better evidence of reducing chronic complications. The main objective of this study is to present a case report addressing the impact of type II diabetes mellitus treatment through non-pharmacological measures based on lifestyle changes (healthy eating and moderate-intensity physical activity). This is a descriptive observational study conducted through medical follow-up in the office and subsequent analysis of the digital medical record of a patient who was followed up at a Basic Health Unit, affiliated with a third-party institution. A critical literature review was conducted using the PubMed, Scielo, and Medline databases, selecting the most relevant articles for the discussion of the clinical case, aiming to understand its relevance and contextualization within the most recent medical literature on this subject. The reported case involves the follow-up of a 53-year-old woman diagnosed with type II diabetes mellitus, who achieved disease remission through non- pharmacological treatment based on calorie-restricted diet and regular physical activity. After 7 months of treatment, the patient lost 22 kg compared to her initial weight, presenting remission of the disease and remaining in remission for 15 years, with glycated hemoglobin values below those considered for the diagnosis of pre- diabetes. The treatment of type II diabetes mellitus aims to prevent, treat, or even reverse disease complications, improving the patient’s quality of life. This case report aims to contribute to the medical literature by reflecting on the impact of non-pharmacological measures in the treatment of type II diabetes mellitus.

Biotechnology Revolution Shaping the Future of Diabetes Management

Introduction: Diabetes mellitus (DM) has a millennia-long history, with early references dating back to ancient Egypt and India. However, it was not until the 20th century that the connection between diabetes and insulin was fully understood. The sequencing of insulin in the 1950s initiated the convergence of biotechnology and diabetes management, leading to the development of recombinant human insulin in 1982. This marked the start of peptide-based therapies in DM. Recombinant peptides for DM treatment: Numerous recombinant peptides have been developed since, starting with modified insulin molecules, with the aim of bettering DM management through fine-tuning the glycemic response to insulin. Peptide-based therapies in DM have expanded substantially beyond insulin to include agonists of Glucagon-like peptide-1 receptor and Glucose-dependent insulinotropic polypeptide receptor, glucagon receptor antagonists, and even peptides exerting multiple receptor agonist effects, for better metabolic control. Insulin pumps, continuous glucose monitoring, and automated insulin delivery systems: The development of modern delivery systems combined with real-time glucose monitoring has significantly advanced diabetes care. Insulin pumps evolved from early large devices to modern sensor-augmented pumps with automated shutoff features and hybrid closed-loop systems, requiring minimal user input. The second-generation systems have demonstrated superior outcomes, proving highly effective in diabetes management. Islet cell transplantation, organoids, and biological pancreas augmentation represent innovative approaches to diabetes management. Islet cell transplantation aims to restore insulin production by transplanting donor beta cells, though challenges persist regarding graft survival and the need for immunosuppression. Organoids are a promising platform for generating insulin-producing cells, although far from clinical use. Biological pancreas augmentation relies on therapies that promote beta-cell (re)generation, reduce stress, and induce immune tolerance. Further biotechnology-driven perspectives in DM will include metabolic control via biotechnology-enabled tools such as custom-designed insulin hybrid molecules, machine-learning algorithms to control peptide release, and engineering cells for optimal peptide production and secretion.

Association between Gamma-Glutamyl Transferase Levels and Pancreatobiliary Cancer Risk in Patients with Diabetes: Evidence from the National Health Insurance Cooperation Health Checkup 2009 to 2012.

Elevated gamma-glutamyl transferase (GGT) levels indicate hepatic dysfunction and have been linked to an increased risk of pancreatobiliary cancers. However, this association, particularly in individuals with diabetes mellitus (DM), requires elucidation. We aimed to examine the association between elevated serum GGT levels and pancreatobiliary cancer risk in patients with diabetes. Our study included data from the National Health Insurance Service (NHIS) database for 2,459,966 adults aged >20 years diagnosed with DM between 2009 and 2012. We examined the association between serum GGT levels and pancreatobiliary cancer risk, considering DM-related factors. Serum GGT levels were categorized into quartiles, and Cox proportional hazards analysis was performed to evaluate the association between serum GGT levels and pancreatobiliary cancer risk. Over a median follow-up period of 7.2 years, 21,795 patients (0.89%) were newly diagnosed with pancreatobiliary cancer. The adjusted hazard ratio for pancreatobiliary cancer in quartiles 2-4 compared with that in quartile 1 was 1.091, 1.223, and 1.554, respectively, demonstrating a significant upward trend (p<0.001). This association remained consistent across all cancer types and was independent of the DM duration or treatment regimen. Elevated serum GGT levels were independently associated with an increased risk of pancreatobiliary cancer, regardless of the duration of DM or the use of oral hypoglycemic agents and insulin. While these findings suggest the potential utility of serum GGT as a biomarker for identifying individuals at higher risk of pancreatobiliary cancer within the diabetic population, further research is needed to validate its clinical applicability.

A Compressive Review on Formulation and Evaluation of Herbal Niosomes containing Phaseolus vulgaris and zingiber officinale for the Treatment of Diabetes Mellitus

This study aimed to formulate and evaluate niosomes containing Phaseolus vulgaris (PV) and Zingiber officinale (ZO) for their antidiabetic activity. Niosomes, non-ionic surfactant vesicles, were prepared using PV and ZO extracts via the thin-film hydration method. The formulations were characterized for particle size, morphology, entrapment efficiency, and in vitro release profile. Antidiabetic activity was assessed through in vitro α-amylase inhibition assay and glucose uptake studies using differentiated 3T3-L1 adipocytes. The formulated niosomes exhibited a mean particle size within the nanometer range, indicating their suitability for drug delivery. Morphological examination revealed spherical vesicles with uniform size distribution. Entrapment efficiency of the bioactive constituents from PV and ZO extracts was found to be satisfactory. In vitro release studies demonstrated sustained release profiles over time, indicative of controlled drug delivery potential. Antidiabetic activity assessment revealed significant α-amylase inhibition by the niosomal formulations compared to free extracts. Furthermore, glucose uptake studies demonstrated enhanced glucose uptake by 3T3-L1 adipocytes treated with niosomes containing PV and ZO extracts compared to untreated cells.

The sale of medicines used for diabetes mellitus treatment in retail segment of Russian pharmaceutical market

Objective: to study the characteristics of the population consumption of medicines for the treatment of diabetes mellitus (DM), sold in the retail sector of the pharmaceutical market of the Russian Federation (RF).Material and methods. The study analyzed data on products assortment and sales volumes for drugs used to treat DM (according to Anatomical Therapeutic Chemical (ATС) classification) trough pharmacies in all federal districts of the RF for the period 2020–2023. In particular, the following ATС groups were studied: A10A, A10B, H04AA and A16AX (thioctic acid), as well as “sibutramine + metformin” combination prescribed to correct obesity in DM patients. The results were obtained on basis of comparative, retrospective, logical, and graphical methods as well as content analysis, data grouping in accordance with ATС groups and descriptive statistics.Results. In the retail sector of the pharmaceutical market of the RF, 54.9 million packages of antidiabetic drugs were sold for 32.4 billion rubles from 2020 to 2023. In the structure of sales in monetary terms, the share of Russian-manufactured drugs amounted to 16–17% approximately, and in physical terms, i.e. by the number of packages, it reached 37–39%. Throughout the analyzed period, the weighted average price (WAP) per 1 package of a drug for DM treatment increased from 472 to 589 rubles. Concurrently, as of year-end 2023, WAP per 1 package of an imported drug was 3 times higher than WAP of a domestic drug (784 and 259 rubles, respectively). In 2023, more than 45% of pharmacy sales in physical terms accrued to drugs of the ATC subgroup A10BA Biguanides (metformin), and about 25% to A10BB Sulfonylurea derivatives (glibenclamide, gliclazide, glimepiride, etc.). In 2023, the highest sales in monetary terms accrued to methsopamine, daphgylflozin, tytochotic acid, empagliflozin and gliclazide. In the structure of retail sales of drugs for DM treatment, fixed combinations accounted for about 15%. Despite an increase in the number of trade names of fixed combinations (from 24 in 2020 to 30 in 2023), their share in the products assortment structure remained insignificant, that did not comply with international recommendations for DM treatment.Conclusion. Using pharmacoepidemiological monitoring tools, the features of the population consumption of drugs prescribed for DM treatment in the retail sector of the pharmaceutical market of the RF were studied in a retrospective aspect (for the period from 2020 to 2023). The contribution of ATC subgroups to the retail sales structure was established. It was revealed that the share of combined drugs was not more than 15% in the total retail sales structure that did not comply with international recommendations on DM treatment.

A Potential Diabetic-Friendly Food Material: Optimization, Nutritional Quality, Structural Characteristics, and Functional Properties of Oat and Purple Potato Fermented by Ganoderma lucidum Mycelium

Dietary intervention is the basis for the treatment of diabetes mellitus. This study employed Ganoderma lucidum (GL) mycelium to ferment a compound medium of oat and purple potato (OPP), optimized fermentation conditions to increase the triterpene content in the resulting product (F-OPPF), and systematically investigated the impact of fermentation on the nutritional quality, structural characteristics, and functional properties of OPP. The results indicated that the triterpene content in F-OPPF significantly increased from 8.53 mg/g to 17.23 mg/g under optimal conditions (temperature: 28 °C, inoculum size: 10%, material quantity: 36 g/250 mL, and fermentation time: day 13). Fermentation resulted in enhanced nutritional quality, with increased contents of protein, soluble protein, crude fiber, ash, mineral elements, essential amino acids, polysaccharides, flavonoids, and total phenols. Mycelium not only enveloped the OPP surface but also penetrated its interior, forming a porous honeycomb-like structure. The types of reactive groups and crystals (C + V-type) were not changed after fermentation, while the crystallinity increased. F-OPPF exhibited positive changes in thermogravimetric properties, antioxidant and hypoglycemic activities, and adsorption capacity of insoluble dietary fiber. Additionally, incorporating F-OPPF into the diet markedly reduced fasting blood glucose levels and promoted weight gain in T2DM rats induced by a high-fat diet and streptozotocin. The fermented groups exhibited improvements in glyco- and lipo-metabolism, oxidative stress, and the function and pathological morphology of the pancreas, liver, and kidneys compared to the unfermented group. Collectively, these findings suggested that GL mycelium fermentation enhanced the nutritional and functional values of OPP, and F-OPPF holds potential as a raw material for developing diabetic-friendly foods.

Knockout of B2M in combination with PD-L1 overexpression protects MSC-derived new islet β cells from graft rejection in the treatment of canine diabetes mellitus

BackgroundThe immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect.MethodsIn this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained.ResultsThe immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site.ConclusionsNew islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.

Obstacles for self-management practices among diabetes patients: A facility-based study from Coastal South India.

Background The purpose of the study was to assess the obstacles faced by diabetes patients in their self-care and determine the factors associated with these obstacles. The management of diabetes mellitus (DM) extends beyond the clinician’s efforts, with the responsibility of the care also being shared by the patient to achieve better treatment outcomes and prevent complications. Self-care management is the most important part of DM treatment, which includes diet, regular exercise, blood glucose monitoring, medication and foot care. Methods A facility-based cross-sectional study was conducted among 107 type 2 DM patients aged &gt;18 years using the Diabetes Obstacles Questionnaire-30. Patients scoring a mean response score &gt;3 were considered to have an obstacle. We included age, gender, socioeconomic status (SES), duration of DM and blood glucose levels as factors for regression analysis and a P value &lt;0.05 was considered to be statistically significant. Results A large majority (64.5%, n = 69) of our participants were aged above 55 years and belonged to lower socio-economic status (65.4%, n = 70). Family history of DM was present in 41% (n=44) of the participants. The median duration of DM among the participant was 10 (4 – 7) years. In our study, the participants faced obstacles for two items in the domains: Support from Friends &amp; Family (mean score: 3.73) and Knowledge of the Disease (mean score: 3.58). A multinominal regression analysis revealed SES was predictive of participants who could not understand information from literature with a P. value of 0.002 (OR: 3.65, CI: 1.60-8.338). Conclusion The two major obstacles to self-management practices that were identified were in the domains of Support from Friends and Family, and Knowledge of the Disease. Socioeconomic status was identified to be a predictive factor associated with the participants who are not able to understand information from the literature.

Identification of TIGAR, a direct proteomic target associated with the hypoglycemic effect of Berberine

Diabetes mellitus is a global chronic metabolic disease and the prevalence of diabetes mellitus is increasing dramatically every year. Berberine (BBR) from Coptidis Rhizoma has potent hypoglycemic effects, however, the specific proteins targeted by berberine that contribute to its hypoglycemic action remain to be elucidated. In this work, TIGAR (TP53-induced glycolysis and apoptosis regulator) was identified as a direct target protein for berberine using activity-based protein profiling (ABPP) and other chemical proteomics techniques with active photoaffinity probes as chemical tools. In addition, the study revealed that berberine-targeted TIGAR attenuated the conversion of fructose-2, 6-bisphosphate to fructose-6-phosphate. This study demonstrated an innovative mechanism by which berberine directly targets TIGAR and its hypoglycemic effects. Therefore, TIGAR emerges as a novel target for the treatment of diabetes mellitus, with TIGAR inhibitors offering a new and promising therapeutic strategy for managing the disease.

Molecular Docking Analysis of Herbal Medicines for Diabetes Mellitus Treatment

Background: Diabetes Mellitus is a global health concern affecting millions of individuals worldwide. It is characterized by hyperglycemia resulting from insufficient insulin production or insulin resistance. Its high prevalence, especially in developing countries, such as Pakistan, demands effective and economically viable treatments. Objectives: The objective of this study was to identify herbal remedies for effectively targeting gluconeogenic enzymes in the treatment of diabetes mellitus. It aimed to explore herbal remedies for providing cost-effective alternatives with lesser side effects for the treatment of diabetes by targeting gluconeogenic enzymes. Methods: The proteins of the already-known diabetic herb Momordica Charantia (Bitter melon) were initially investigated through molecular docking. Then, the proteins similar to the bestdocked protein of Momordica Charactia were identified, and their molecular docking analysis was performed. Results: The results showed three plants having similar proteins to the Momrodica Charantia best-docked protein, namely Luffa Aegyptiaca (sponge gourd), Cucumis Sativus (cucumber), and Cucurbita Maxima (Pumpkin). The molecular docking analysis of these proteins revealed Cucumis Sativus (Cucumber) as a potential herbal candidate for the treatment of diabetes mellitus. Conclusion: The results of this study highlight the potential of Cucumis Sativus (Cucumber) for treating diabetes mellitus by targeting gluconeogenic enzymes. However, further research is necessary regarding the therapeutic potential of cucumber.

Ethnopharmacological Insights into Diabetes Management: Exploring Medicinal Flora of Shivalik range of Himalaya in Uttarakhand

Diabetes mellitus is a chronic metabolic disorder which is commonly found life-threatening disease and it continuously reducing the life expectancy. It is characterized by hyperglycaemia (raised blood sugar level) resulting from defects in insulin secretion, action, or both. Since thousands of years, medicinal plants are being used by our ancestors for the prevention, treatment or even cure the diabetes mellitus. Utilization of these herbal plants is increasing rapidly last two to three decades due to their lesser toxicity and cost effectiveness property as compared to synthetic drugs. In this review, approximately 30 medicinal plants were described which are native to India and traditionally used by the people living in shivalik range of Himalaya in Uttarakhand (specially Dehradun &amp; Haridwar) for the treatment of diabetes mellitus. The data about these plants was collected from science direct, PubMed, web of science, scopus, mdpi, google scholar and different other search engines and websites. This review was conferred in a systematic way as it includes botanical name, family, vernacular name, parts used and pharmacological uses of plants in a tabulated form. There are various scientific evidences behind the uses of some medicinal plants which have been mentioned along with the summary of individual medicinal plant. In this review, all the plants and herbs are easily available in these regions of Uttarakhand and local people traditionally uses these plants as vegetable, seasoning, flavouring and usually consume as a part of their diet. There are some limitations of phytotherapy which limit it to completely replace the allopathic therapy as less bioavailability, less rate of absorption and slow rate of dissolution. But by using various advanced dosage forms (phytosomes, neosomes, liposomes, nanoparticles, nanobubbles, nano diamonds, nanosphere etc.) and method of delivery (various invasive and non-invasive methods) which can bypass these all problems associated with the potency and efficacy of phytochemicals.

Molecular modeling and synthesis of novel benzimidazole-derived thiazolidinone bearing chalcone derivatives: a promising approach to develop potential anti-diabetic agents.

Diabetes mellitus (DM) is a disorder which is raised at the alarming level and it is characterized by the hyperglycemia results from the impaired action of insulin, production of insulin or both of these simultaneously. Consequently, it causes problems or failure of different body organs such as kidneys, heart, eyes, nerve system. Since this disease cannot be completely cured until now, we aimed to design series of enzymes inhibitors and tested them for DM treatment. In this series, benzimidazole-based thiazolidinone bearing chalcone derivatives completed in a four step reaction and their structures were confirmed through various spectroscopic techniques. A significant efficacy on antidiabetic enzymes was observed, with IC50 values ranging from 25.05±0.04 to 56.08±0.07 μM for α-amylase and 22.07±0.02 to 53.06±0.07 μM for α-glucosidase. The obtained results were compared to those of the standard glimepiride drug (IC50=18.05±0.07 µM for α-amylase and IC50=15.02±0 .03 µM for α-glucosidase). The synthesized compounds showed promising antidiabetic potency. Moreover, a molecular docking study was conducted on the most active analogs of the compounds to better understand their interactions with the active sites of the targeted enzymes.

Antidiabetic potential of four species of Termitomyces mushrooms from Nepal

People use mushrooms to treat diabetes mellitus. We studied the antidiabetic potential of four Termitomyces mushrooms using porcine pancreatic α-amylase inhibitory activity and alloxan-induced diabetic mice. Methanolic extracts of all Termitomyces mushrooms were effective in inhibiting α-amylase activity. T. striatus forma ochraceus showed the highest α-amylase inhibitory activity of 61.4% (200 g/ml). When we administered intraperitoneal doses of Termitomyces extracts (250 and 500 mg/kg) to alloxan-induced diabetes mice (30–35 g), we observed a weight loss in diabetic control mice compared to diabetic mice. At the end of the 15 days, diabetic control mice lost more weight with the administration dose of 500 mg/kg than that of 250 mg/kg Termitomyces extracts. Monitoring blood glucose levels for 15 days revealed that 500 mg/kg significantly reduced blood glucose levels compared to 250 mg/kg. In conclusion, Termitomyces species were effective in decreasing α-amylase activity and reducing blood sugar levels in alloxan-induced diabetic mice.

Anti-diabetic effects of marine natural products through redox modulation via Nrf2/HO-1 cytoprotective pathways

Diabetes mellitus (DM), a major global health concern, is a chronic metabolic disorder. Bioactive compounds sourced from numerous marine natural products recently have drawn attention as novel therapeutic approaches. Considering these chemicals and their role in cellular redox modulation by involving the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, the current study attempts to highlight their anti-diabetic effects and the molecular mechanisms involved. Reactive oxygen species (ROS)-mediated oxidative stress, inflammation, and cellular damage are linked to most human pathologies specifically DM. The Nrf2/HO-1 pathway is a key defense mechanism developed by the cells to combat ROS burst. Marine natural compounds have strong pharmacological potential in triggering cellular antioxidant defense mechanisms by declining oxidative damage and inflammation linked to DM. How marine natural products potentially alleviate DM specifically type 2 diabetes (T2D) and its related issues is especially focused on. The literature was thoroughly analyzed to open a discussion about specific marine compounds and their well-established anti-diabetic effects to elucidate possible therapeutic applications. Furthermore, opportunities and the pros and cons of using these marine bioactive compounds as complementary treatment for DM are also discussed. The diverse characteristics of marine natural products, specifically with regard to redox control, offer promising opportunities for drug discovery and therapeutic interventions in clinical trials.

Retroperitoneal pancreas transplantation with a Roux-en-Y duodenojejunostomy for exocrine drainage

BackgroundPancreatic transplantation is the only definitive surgical treatment for diabetes mellitus. Currently, most transplant centers use enteric exocrine drainage of pancreatic secretions; however, experts disagree on which part of the gastrointestinal tract is preferable for enteric anastomosis. We analyzed the outcomes of retroperitoneal pancreatic transplantation with enteric drainage of pancreatic secretions.Materials and methodsWe evaluated the outcomes of 60 simultaneous retroperitoneal pancreas-kidney transplantations. Based on the type of enteric anastomosis, the patients were divided into two groups: the study group consisted of 10 patients who underwent enteric drainage via Roux-en-Y duodenojejunostomy, and the control group included 50 patients who underwent exocrine drainage via duodenoduodenal anastomosis. No statistically significant differences were observed between the groups in terms of the main parameters.ResultsThe rate of surgical complications did not differ significantly between the groups (p > 0.05). Clavien IVb complications occurred only in the control group (n = 4.8%). The in-hospital pancreatic graft survival rate in both groups was 80%, whereas the recipient survival rates were 90% and 84%, in the study and control groups, respectively (p < 0.05).ConclusionRetroperitoneal pancreatic transplantation with exocrine drainage via a Roux-en-Y duodenojejunostomy is an effective alternative technique that reduces the rate of severe surgical complications.

Integrating Metabolomic Analysis, Network Pharmacology, and Molecular Docking to Underlying Pharmacological Mechanism and Ethnobotanical Rationalization for Diabetes Mellitus: Study on Medicinal Plant Fibraurea tinctoria Lour.

Fibraurea tinctoria Lour. has long been used in traditional medicine to treat diabetes mellitus (DM). However, a comprehensive scientific understanding of its potential active compounds and underlying pharmacological mechanisms still needs to be unveiled. This study, therefore, presents a novel approach by integrating metabolomic profiling, pharmacological network, and molecular docking analysis to investigate the potential of F. tinctoria as antidiabetes mellitus. Active compounds were obtained through analysis using ultrahigh-performance liquid chromatography-quadrupole-orbital ion trap-high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and screening of active compounds using Lipinski rule of five and ADMET parameters. Potential targets of F. tinctoria compounds and DM-related targets were retrieved from public databases, such as DisGeNET, GeneCards, OMIM, PharmaGKB, and TTD. The targets' gene ontology (GO) was created using DAVID and protein-protein interactions using STRING. The plant-organ-compound-target-disease network was constructed using Cytoscape. Then, molecular docking analysis predicted and verified the interactions of essential bioactive compounds of F. tinctoria and DM core targets. The network pharmacology approach identified 35 active compounds, 565 compound-related targets, and 17,289 DM-related targets. EGFR, HSP90AA1, ESR1, HSP90AB1, and GSK3B were the core targets, whereas isolariciresinol, cubebin, corypalmine, (-)-8-oxocanadine, and (+)-N-methylcoclaurine were the most active compounds of F. tinctoria with DM potential. GO functional enrichment analysis revealed 483 biological processes, 485 cellular components, and 463 molecular functions. REACTOME pathway enrichment analysis yielded 463 significantly enriched signaling pathways. Of these pathways, the cytokine signaling in the immune system pathway may play a key role in treating DM. The results of molecular docking analysis showed that the core targets of DM, such as 5gnk, 3o0i, 6psj, 5ucj, and 1q5k, bind stably to the analyzed bioactive compounds of F. tinctoria. This study provides significant insights into the potential mechanism of F. tinctoria in treating DM. The main active compounds of F. tinctoria were found to interact with the core targets (EGFR, HSP90AA1, ESR1, HSP90AB1, and GSK3B) through the cytokine signaling pathway in the immune system, suggesting a potential therapeutic pathway for DM. However, it is essential to note that these findings are preliminary, and further research is necessary to validate them. Those research studies could involve invitro and invivo studies to confirm the bioactivity of the identified compounds and their interactions with the core targets. When the findings are confirmed, they could have significant clinical implications, potentially leading to developing new therapeutic strategies for DM.

Lingguizhugan decoction alleviates gestational diabetes mellitus by modulating the PI3K-AKT pathway and oxidative stress: Network pharmacology and experimental evidence.

The Lingguizhugan decoction (LGZGD) is a promising traditional Chinese medicine for the treatment of gestational diabetes mellitus (GDM). However, its bioactive compounds and therapeutic mechanisms remain unknown. The main chemical composition of LGZGD was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Furthermore, the underlying mechanisms of LGZGD against GDM were elucidated through network pharmacology and molecular docking. The therapeutic efficacy and targets of LGZGD were further confirmed via an in vitro GDM model (high glucose [HG]-treated HTR-8/SVneo cells). Four compounds of LGZGD, namely, cinnamaldehyde, glycyrrhizic acid, 2-atractylenolide, and pachymic acid, were detected. A total of 26 targets for LGZGD treating GDM were obtained, which were mainly involved in oxidative stress and the PI3K-AKT signaling pathway. The protein-protein interaction (PPI) network unveiled that AKT1, TLR4, TP53, and NOS3 were hub therapeutic targets. Molecular docking showed that these targets had strong affinity with key compounds. In vitro experiments confirmed that LGZGD treatment promoted HG-induced cell viability, migration, and invasion ability while inhibited the apoptosis rate and oxidative stress. Mechanically, western blot revealed that LGZGD may protect HG-treated cells by activating the PI3K-AKT pathway and suppressing TLR4 expression. Our study preliminarily explored the mechanism of LGZGD in GDM treatment, providing a scientific basis for the clinical application of LGZGD.