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1.
Sci Rep ; 14(1): 16658, 2024 07 19.
Article de Anglais | MEDLINE | ID: mdl-39030286

RÉSUMÉ

Neokestose is considered to have a prebiotic function. However, the physiological activity of neokestose remains unknown. Neokestose has a blastose, a sucrose analog, in its structure. We previously demonstrated that oral administration of blastose to diabetic rats suppressed the increase in plasma glucose (PG) concentration after sucrose administration. Therefore, neokestose might have a similar effect. In this study, we investigated the effects of neokestose on PG concentrations and the mechanism of its action. We first administered neokestose orally to streptozotocin-induced diabetic rats and observed that the expected consequent increase in PG concentration was significantly suppressed. Next, we examined the inhibitory effect of neokestose on glycosidase activity, but observed only a slight inhibitory effect. Therefore, we hypothesized that neokestose might be hydrolyzed by gastric acid to produce blastose. We performed an acid hydrolysis of neokestose using artificial gastric juice. After acid hydrolysis, peaks corresponding to neokestose and its decomposition products including blastose were observed. Therefore, we suggest that neokestose and blastose, a decomposition product, synergistically inhibit glycosidase activity. These findings support the potential use of neokestose as a useful functional oligosaccharide that can help manage plasma glucose concentrations in patients with diabetes mellitus.


Sujet(s)
Glycémie , Diabète expérimental , Saccharose , Animaux , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Diabète expérimental/métabolisme , Glycémie/métabolisme , Administration par voie orale , Rats , Mâle , Saccharose/analogues et dérivés , Saccharose/administration et posologie , Streptozocine , Glycosidases/métabolisme , Hydrolyse , Oligosaccharides/pharmacologie , Oligosaccharides/administration et posologie
2.
Drug Des Devel Ther ; 18: 1981-1996, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855535

RÉSUMÉ

Background: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.


Sujet(s)
Diabète expérimental , Hypoglycémiants , Métabolome , Rat Sprague-Dawley , Streptozocine , Animaux , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Diabète expérimental/métabolisme , Rats , Hypoglycémiants/pharmacologie , Mâle , Métabolome/effets des médicaments et des substances chimiques , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Alimentation riche en graisse , Médicaments issus de plantes chinoises/pharmacologie
3.
Pak J Pharm Sci ; 37(2(Special)): 459-462, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38822550

RÉSUMÉ

The purpose of this study was to examine the potential hypoglycemic effects of administering ginger (Zingiber officinale) and garlic (Allium sativum) to rats with induced type 2 diabetes. A total of forty-five male adult albino rats were randomly assigned to five groups. The groups were named Normal Control, Diabetic Control, Ginger group, Garlic group and a combination group of ginger and garlic. Diabetes was produced in all groups, except the normal control group, using an intraperitoneal injection of streptozotocin at a dosage of 60 mg/body weight. During the course of two months, rats were administered varying amounts of ginger and garlic powders as part of their treatment After the experiment concluded, measurements were taken for glycated hemoglobin, serum glucose, insulin, cholesterol, high density protein, low density protein and liver glycogen levels. These groups exhibited considerably greater serum insulin and high-density lipoprotein concentrations (P<0.05) compared to the diabetic control group. Conversely, body weight, fasting blood glucose, total cholesterol, low density lipoprotein, and glycated hemoglobin levels were significantly lower (P<0.05) in all groups compared to the diabetic control group. A statistically significant increase (P<0.05) increase shown in liver glycogen levels. This study proposes that the utilization of ginger and garlic powders improve the condition of type 2 diabetes and maybe reduce the risk of subsequent diabetic complications.


Sujet(s)
Glycémie , Diabète expérimental , Ail , Hypoglycémiants , Insuline , Poudres , Zingiber officinale , Animaux , Ail/composition chimique , Zingiber officinale/composition chimique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Mâle , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Rats , Insuline/sang , Diabète de type 2/traitement médicamenteux , Diabète de type 2/sang , Hémoglobine glyquée/métabolisme , Extraits de plantes/pharmacologie , Phytothérapie , Glycogène hépatique/métabolisme , Streptozocine
4.
Vet Q ; 44(1): 1-14, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38943615

RÉSUMÉ

Background: Mistletoe is an herb that grows on duku plants (Lancium demosticum) and is known as benalu duku (BD) in Indonesia. It is predicted to have benefits such as anticancer or antiviral properties, and it is also thought to have anti-diabetic pharmacological activity. Quercetin-like compounds (QLCs) are secondary metabolites with antidiabetic activity that are expected to lower blood sugar levels in animals after oral administration.Objective: This study aimed to analyze the ability of QLCs to reduce random blood sugar levels using experimental animals as clinical models.Material and methods: The research method used was exploratory, which used a before-after test model, and observations were made on the random blood sugar levels after treatment. Secondary metabolites were extracted from BD leaves, which were then screened. Diabetes was induced in 30 rats (Rattus norvegicus) by the administration of streptozotocin at 0.045 mg/g body weight daily for 2 days. The antidiabetic effects of the secondary metabolite at doses of 0.5 mg/kg body weight (twice a day) when administered orally for up to 5 days were tested in diabetic rats. The random sugar levels (mg/dL) were measured using a One Touch Ultra Plus medical device for observation of randomized blood sugar levels. Results and novelty: The results revealed that the secondary metabolite, as an analyte from the BD leaf extract, can significantly reduce random blood sugar levels.Conclusion: The secondary metabolite extracted from BD, could be used to treat diabetes in rats.


Sujet(s)
Glycémie , Diabète expérimental , Hypoglycémiants , Extraits de plantes , Quercétine , Animaux , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Rats , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Hypoglycémiants/administration et posologie , Quercétine/pharmacologie , Quercétine/analogues et dérivés , Quercétine/usage thérapeutique , Glycémie/analyse , Glycémie/effets des médicaments et des substances chimiques , Mâle , Extraits de plantes/pharmacologie , Extraits de plantes/administration et posologie , Gui/composition chimique , Administration par voie orale , Feuilles de plante/composition chimique
5.
J Diabetes Res ; 2024: 4538199, 2024.
Article de Anglais | MEDLINE | ID: mdl-38919263

RÉSUMÉ

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF-α, IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis.


Sujet(s)
Diabète expérimental , Diabète de type 2 , Neuropathies diabétiques , Hormones peptidiques , Humains , Diabète de type 2/complications , Diabète de type 2/sang , Neuropathies diabétiques/sang , Neuropathies diabétiques/étiologie , Animaux , Mâle , Adulte d'âge moyen , Femelle , Diabète expérimental/complications , Diabète expérimental/sang , Souris , Sujet âgé , Hormones peptidiques/sang , Agranulocytes/métabolisme , Seuil nociceptif , Chine/épidémiologie , Souris de lignée C57BL
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124653, 2024 Nov 05.
Article de Anglais | MEDLINE | ID: mdl-38901232

RÉSUMÉ

The number of people suffering from type 2 diabetes has rapidly increased. Taking into account, that elevated intracellular lipid concentrations, as well as their metabolism, are correlated with diminished insulin sensitivity, in this study we would like to show lipids spectroscopy markers of diabetes. For this purpose, serum collected from rats (animal model of diabetes) was analyzed using Fourier Transformed Infrared-Attenuated Total Reflection (FTIR-ATR) spectroscopy. Analyzed spectra showed that rats with diabetes presented higher concentration of phospholipids and cholesterol in comparison with non-diabetic rats. Moreover, the analysis of second (IInd) derivative spectra showed no structural changes in lipids. Machine learning methods showed higher accuracy for IInd derivative spectra (from 65 % to 89 %) than for absorbance FTIR spectra (53-65 %). Moreover, it was possible to identify significant wavelength intervals from IInd derivative spectra using random forest-based feature selection algorithm, which further increased the accuracy of the classification (up to 92 % for phospholipid region). Moreover decision tree based on the selected features showed, that peaks at 1016 cm-1 and 2936 cm-1 can be good candidates of lipids marker of diabetes.


Sujet(s)
Marqueurs biologiques , Diabète expérimental , Apprentissage machine , Spectroscopie infrarouge à transformée de Fourier/méthodes , Animaux , Diabète expérimental/sang , Marqueurs biologiques/sang , Mâle , Lipides/sang , Rats , Rat Wistar , Phospholipides/sang , Phospholipides/analyse , Diabète de type 2/sang
7.
J Proteome Res ; 23(7): 2619-2628, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38910295

RÉSUMÉ

Chromatography-mass spectrometry-based lipidomics represents an essential tool for elucidating lipid dysfunction mechanisms and is extensively employed in investigating disease mechanisms and identifying biomarkers. However, the detection of low-abundance lipids in biological matrices, along with cumbersome operational procedures, complicates comprehensive lipidomic analyses, necessitating the development of highly sensitive, environmentally friendly, and automated methods. In this study, an online phase transition trapping-supercritical fluid extraction-chromatography-mass spectrometry (PTT-SFEC-MS/MS) method was developed and successfully applied to plasma lipidomics analysis in Type 1 diabetes (T1D) rats. The PTT strategy captured entire extracts at the column head by converting CO2 from a supercritical state to a gaseous state, thereby preventing peak spreading, enhancing peak shape for precise quantification, and boosting sensitivity without any sample loss. This method utilized only 5 µL of plasma and accomplished sample extraction, separation, and detection within 27 min. Ultimately, 77 differential lipids were identified, including glycerophospholipids, sphingolipids, and glycerolipids, in T1D rat plasma. The results indicated that the progression of the disease might be linked to alterations in glycerophospholipid and sphingolipid metabolism. Our findings demonstrated a green, highly efficient, and automated method for the lipidomics analysis of biological samples, providing a scientific foundation for understanding the pathogenesis and diagnosis of T1D.


Sujet(s)
Chromatographie en phase supercritique , Diabète de type 1 , Lipidomique , Spectrométrie de masse en tandem , Animaux , Lipidomique/méthodes , Spectrométrie de masse en tandem/méthodes , Rats , Chromatographie en phase supercritique/méthodes , Diabète de type 1/sang , Diabète de type 1/métabolisme , Lipides/sang , Lipides/composition chimique , Diabète expérimental/sang , Diabète expérimental/métabolisme , Mâle , Rat Sprague-Dawley , Transition de phase , Marqueurs biologiques/sang , Sphingolipides/sang , Sphingolipides/analyse , Sphingolipides/isolement et purification
8.
Biomed Pharmacother ; 177: 117053, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38945083

RÉSUMÉ

OBJECTIVE: The main objective of this study was to find if thiamine disulfide (TD) lowers blood glucose level and improves insulin resistance (IR) in liver and muscle in rats with chronic type 1 diabetes (T1DM) using euglycemic-hyperinsulinemic clamp technique. METHODS: A total of fifty male Wistar rats were assigned to five groups consisted of: non-diabetic control (NDC), diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with both TD and insulin (D-insulin+TD). Diabetes was induced by a 60 mg/kg dose of streptozotocin. Blood glucose levels, pyruvate tolerance test (PTT), intraperitoneal glucose tolerance test (IPGTT), levels of glycosylated hemoglobin (HbA1c), glucose infusion rate (GIR), liver and serum lipid profiles, liver glycogen stores, liver enzymes ([ALT], [AST]), and serum calcium and magnesium levels. were evaluated. Additionally, gene expression levels of phosphoenolpyruvate carboxykinase (Pepck), forkhead box O1 (Foxo1), and glucose transporter type 4 (Glut4) were assessed in liver and skeletal muscle tissues. RESULTS: Blood glucose level was reduced by TD treatment. In addition, TyG index, HOMA-IR, serum and liver lipid profiles, HbA1c levels, and expressions of Foxo1 and Pepck genes were decreased significantly (P<0.05) in all the treated groups. However, TD did not influence Glut4 gene expression, but GIR as a critical index of IR were 5.0±0.26, 0.29±0.002, 1.5±0.07, 0.9±0.1 and 1.3±0.1 mg.min-1Kg-1 in NDC, DC, D-TD, D-insulin and D-insulin+TD respectively. CONCLUSIONS: TD improved IR in the liver primarily by suppressing gluconeogenic pathways, implying the potential use of TD as a therapeutic agent in diabetes.


Sujet(s)
Glycémie , Diabète expérimental , Diabète de type 1 , Insulinorésistance , Foie , Rat Wistar , Thiamine , Animaux , Mâle , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques , Diabète expérimental/traitement médicamenteux , Diabète expérimental/métabolisme , Diabète expérimental/sang , Diabète de type 1/traitement médicamenteux , Diabète de type 1/sang , Diabète de type 1/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Rats , Thiamine/pharmacologie , Thiamine/administration et posologie , Transporteur de glucose de type 4/métabolisme , Insuline/sang , Transduction du signal/effets des médicaments et des substances chimiques , Phosphoenolpyruvate carboxykinase (GTP)/métabolisme , Phosphoenolpyruvate carboxykinase (GTP)/génétique , Phosphoenolpyruvate carboxykinase (ATP)/métabolisme , Streptozocine , Protéine O1 à motif en tête de fourche , Protéines et peptides de signalisation intracellulaire
9.
Biochem Pharmacol ; 225: 116306, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38782076

RÉSUMÉ

Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.


Sujet(s)
Diabète de type 2 , Facteurs de croissance fibroblastique , Métabolomique , Facteurs de croissance fibroblastique/métabolisme , Facteurs de croissance fibroblastique/sang , Animaux , Diabète de type 2/métabolisme , Diabète de type 2/traitement médicamenteux , Diabète de type 2/sang , Métabolomique/méthodes , Souris , Mâle , Glycémie/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Hypoglycémiants/usage thérapeutique , Hypoglycémiants/administration et posologie , Diabète expérimental/métabolisme , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang
10.
Biol Pharm Bull ; 47(5): 1043-1053, 2024.
Article de Anglais | MEDLINE | ID: mdl-38811190

RÉSUMÉ

Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.


Sujet(s)
Diabète expérimental , Diabète de type 2 , Microbiome gastro-intestinal , Hypoglycémiants , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Mâle , Diabète de type 2/traitement médicamenteux , Diabète de type 2/métabolisme , Diabète de type 2/microbiologie , Diabète expérimental/traitement médicamenteux , Diabète expérimental/métabolisme , Diabète expérimental/sang , Souris , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Alimentation riche en graisse/effets indésirables , Glycémie/effets des médicaments et des substances chimiques , Triterpènes/pharmacologie , Triterpènes/usage thérapeutique , Récepteur de type Toll-4/métabolisme , Endotoxémie/traitement médicamenteux , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme
11.
Biomed Pharmacother ; 175: 116780, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38781864

RÉSUMÉ

Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.


Sujet(s)
Glycémie , Diabète expérimental , Diabète de type 2 , Hypoglycémiants , Métabolomique , Pueraria , Rat Sprague-Dawley , Animaux , Pueraria/composition chimique , Mâle , Rats , Diabète de type 2/traitement médicamenteux , Diabète de type 2/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Hypoglycémiants/pharmacologie , Hypoglycémiants/administration et posologie , Diabète expérimental/traitement médicamenteux , Diabète expérimental/métabolisme , Diabète expérimental/sang , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques , Administration par voie orale , Extraits de plantes/pharmacologie , Isoflavones/pharmacologie , Insuline/sang , Insuline/métabolisme , Lipides/sang
12.
J Med Life ; 17(2): 217-225, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38813352

RÉSUMÉ

Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many attempts have been made to create oral formulations, especially using nanoparticles (NPs). The aim of this study was to compare the hypoglycemic effect of insulin-loaded NPs to that of subcutaneous insulin in an in vivo rat model of diabetes. We used biodegradable D-α-tocopherol polyethylene glycol succinate-emulsified, chitosan-capped poly(lactic-co-glycolic acid) NPs loaded with soluble human insulin in a dose of 20 IU/kg body weight, and examined the physical characteristics of NPs in vivo and in vitro. Serum glucose levels were reduced after 6 h, but the difference was not significant compared to subcutaneous insulin; at 12 h and 24 h, insulin levels were significantly higher in rats treated with NPs than in rats treated with subcutaneous insulin. There was no significant difference in serum insulin levels at 12 h and 24 h compared to non-diabetic rats. Our findings suggest that chitosan-based NPs are able to maintain good glycemic control for up to 24 h and can be considered a potential carrier for oral insulin delivery.


Sujet(s)
Diabète expérimental , Hyperglycémie , Insuline , Nanoparticules , Streptozocine , Animaux , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Insuline/sang , Insuline/administration et posologie , Rats , Administration par voie orale , Mâle , Hyperglycémie/traitement médicamenteux , Chitosane/composition chimique , Glycémie , Hypoglycémiants/administration et posologie , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Modèles animaux de maladie humaine , Rat Sprague-Dawley
13.
J Diabetes Res ; 2024: 1222395, 2024.
Article de Anglais | MEDLINE | ID: mdl-38725443

RÉSUMÉ

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.


Sujet(s)
Glycémie , Diabète expérimental , Diabète de type 2 , Néphropathies diabétiques , Inflammation , Inuline , Animaux , Mâle , Souris , Glycémie/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Azote uréique sanguin , Diabète expérimental/sang , Diabète expérimental/complications , Diabète expérimental/traitement médicamenteux , Diabète de type 2/sang , Diabète de type 2/complications , Diabète de type 2/traitement médicamenteux , Néphropathies diabétiques/sang , Néphropathies diabétiques/traitement médicamenteux , Néphropathies diabétiques/étiologie , Alimentation riche en graisse , Acides gras volatils/métabolisme , Inflammation/traitement médicamenteux , Inuline/pharmacologie , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Rein/anatomopathologie , Métabolomique , Souris de lignée ICR , Stress oxydatif/effets des médicaments et des substances chimiques
14.
Int J Pharm ; 659: 124250, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38777304

RÉSUMÉ

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.


Sujet(s)
Anti-inflammatoires , Glycémie , Diabète expérimental , Hypoglycémiants , Insuline , Polyosides , Animaux , Polyosides/administration et posologie , Polyosides/composition chimique , Glycémie/effets des médicaments et des substances chimiques , Glycémie/analyse , Administration par voie orale , Insuline/administration et posologie , Insuline/pharmacocinétique , Hypoglycémiants/administration et posologie , Hypoglycémiants/pharmacocinétique , Hypoglycémiants/pharmacologie , Souris , Anti-inflammatoires/administration et posologie , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/pharmacocinétique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Mâle , Vitamine B12/administration et posologie , Nanoparticules/administration et posologie , Libération de médicament , Vecteurs de médicaments/composition chimique , Humains
15.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2783-2797, 2024 May.
Article de Chinois | MEDLINE | ID: mdl-38812179

RÉSUMÉ

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.


Sujet(s)
Médicaments issus de plantes chinoises , Rat Sprague-Dawley , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/pharmacocinétique , Chromatographie en phase liquide à haute performance/méthodes , Animaux , Rats , Mâle , Humains , Foie/effets des médicaments et des substances chimiques , Foie/composition chimique , Foie/métabolisme , Spectrométrie de masse/méthodes , Rein/effets des médicaments et des substances chimiques , Rein/composition chimique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Diabète/traitement médicamenteux
16.
Pak J Pharm Sci ; 37(1): 71-78, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-38741402

RÉSUMÉ

Diabetes mellitus, recognized by elevated glucose level in the body fluids is commonly caused by less insulin production or its action. To overcome the complications of diabetes, chemical drugs are never preferred over herbal medicines. Present study was designed to find out the anti-diabetic and health-promoting effects of ethanolic leaf extracts of Cucumis melo and Citrullus lanatus in induced-diabetic albino rats. Thirty male albino rats were bought from the animal house of the university and divided randomly into five feeding groups (n=6). Diabetes was induced in rats of groups A, B, C & D by a single dose of intra-peritoneal injection of streptozotocin (55 mg/Kg), whereas, the rats of group E were considered as control. The rats of groups A, B & C were fed basal diet supplemented with plant extracts (150mg/Kg body weight), whereas; only basal diet was offered to rats of groups D & E. After 28 days of the experiment, blood was collected for biochemical analysis. Results revealed that body weight, glucose, AST, ALB, GGT, HDL, cholesterol, triglyceride, urea and creatinine level differed significantly among treatment groups. It was therefore concluded that ethanolic leaf extracts of Cucumis melo and Citrullus lanatus can be used separately or in combination for the management of diabetes.


Sujet(s)
Glycémie , Citrullus , Cucumis melo , Diabète expérimental , Hypoglycémiants , Lipides , Extraits de plantes , Animaux , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Extraits de plantes/pharmacologie , Cucumis melo/composition chimique , Mâle , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Citrullus/composition chimique , Rats , Hypoglycémiants/pharmacologie , Hypoglycémiants/isolement et purification , Lipides/sang , Feuilles de plante/composition chimique , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme , Streptozocine
17.
Pak J Pharm Sci ; 37(1): 163-171, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-38741413

RÉSUMÉ

Medicinal plants contain a wide variety of bioactive phytoconstituents which can serve as new therapeutic agents for several diseases. This study examines the antidiabetic potential of Aitchisonia rosea in alloxan-induced diabetic rats and identifies its bioactive phytoconstituents using GC-MS. In vitro, antidiabetic potential was established using the α-amylase inhibition assay. In vivo, antidiabetic potential was investigated by employing the oral glucose tolerance test (OGTT). GC-MS analysis was used to identify the bioactive phytoconstituents. The in vitro and in vivo tests showed that the aqueous extract of A. rosea possesses better antidiabetic potential. The α-amylase inhibition assay highlighted an IC50 value of 134.87µg/ml. In an oral glucose tolerance test, rats given an aqueous A. rosea extract significantly lowered their blood sugar levels significant reduction in the blood glucose concentration was observed in the oral glucose tolerance test in rats treated with the aqueous A. rosea extract. GC-MS investigation revealed many phytoconstituents, with serverogenin acetate and cycloheptasiloxane tetradecamethyl being important antidiabetic agents. This study found anti-diabetic properties in A. rosea extract. The phytochemical and GC-MS investigation also found serverogenin acetate and cycloheptasiloxane tetradecamethyl, which could be used to develop new antidiabetic drugs.


Sujet(s)
Glycémie , Diabète expérimental , Chromatographie gazeuse-spectrométrie de masse , Hypoglycémiants , Parties aériennes de plante , Extraits de plantes , Animaux , Hypoglycémiants/pharmacologie , Hypoglycémiants/isolement et purification , Hypoglycémiants/composition chimique , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Diabète expérimental/induit chimiquement , Parties aériennes de plante/composition chimique , Mâle , Glycémie/effets des médicaments et des substances chimiques , Rats , Hyperglycémie provoquée , alpha-Amylases/antagonistes et inhibiteurs , alpha-Amylases/métabolisme , Rat Wistar , Composés phytochimiques/pharmacologie , Composés phytochimiques/analyse , Alloxane
18.
Pak J Pharm Sci ; 37(2): 291-296, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38767095

RÉSUMÉ

Mangiferin, a key bioactive constituent in Gentiana rhodantha, has a favorable impact on reducing blood sugar. A selective and sensitive UPLC MS/MS approach was developed for determining mangiferin in diabetic rats. Employing acetonitrile protein precipitation, chromatographic separation utilized a 2.1×50 mm, 3.5µm C18 column with a mobile phase of 0.1% formic acid aqueous and 5mM ammonium acetate (A, 45%) and acetonitrile (B, 55%) at a 0.5mL min-1 flow rate. Quantification, employing the multiple reaction monitoring (MRM) mode, focused on precursor-to-product ion transitions at m/z 447.1→271.1 for baicalin m/z and 421.0→301.0 for mangiferin. Calibration curves demonstrated linearity in the 1.00~100ng/mL range, with a lower quantification limit for rat plasma set at 1.00ng/mL. Inter- and intra-day accuracies spanned -9.1% to 8.5% and mangiferin mean recovery varied from 82.3% to 86.7%. The adeptly utilized UPLC-MS/MS approach facilitated the exploration of mangiferin pharmacokinetics in diabetic rats.


Sujet(s)
Diabète expérimental , Gentiana , Extraits de plantes , Spectrométrie de masse en tandem , Xanthones , Animaux , Xanthones/pharmacocinétique , Xanthones/sang , Xanthones/administration et posologie , Diabète expérimental/sang , Diabète expérimental/traitement médicamenteux , Spectrométrie de masse en tandem/méthodes , Mâle , Chromatographie en phase liquide à haute performance/méthodes , Extraits de plantes/pharmacocinétique , Extraits de plantes/administration et posologie , Extraits de plantes/sang , Administration par voie orale , Rats , Gentiana/composition chimique , Rat Sprague-Dawley , Streptozocine , Reproductibilité des résultats ,
19.
Pak J Pharm Sci ; 37(2): 307-314, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38767097

RÉSUMÉ

Long-lasting hyperglycemia can potentially cause damage to organs such as the kidneys, liver and pancreas. Glimepiride (GLIM), as a drug of choice in the treatment of diabetes mellitus (DM), has the risk of decreasing the functioning of organs such as the kidneys, liver and pancreas. Black rice bran ethanol extract (EEBRB) with antioxidant content has been shown to protect the kidney, liver and pancreas organs. The aim of this study was to establish the effect of EEBRB on lowering fasting blood glucose (FBG) and protecting several organs after GLIM administration in alloxan (ALX)-induced hyperglycemic rats. A total of 20 rats were divided into 4 groups and treated for 21 days treatments using following preparations: normal control (NC), diabetic group (DC), GLIM 1 mg/ kgBW and combination of glimepiride 1mg/kgBW and EEBRB 50 mg/KgBW (GLBR). The results showed that the GLBR was able to lower blood glucose levels back to normal (<126 mg/dL) and protect kidney, liver and pancreas cells by increasing the amount in normal cells.


Sujet(s)
Glycémie , Diabète expérimental , Hypoglycémiants , Rein , Foie , Oryza , Pancréas , Extraits de plantes , Sulfonylurées , Animaux , Sulfonylurées/pharmacologie , Extraits de plantes/pharmacologie , Extraits de plantes/isolement et purification , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Glycémie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Oryza/composition chimique , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme , Hypoglycémiants/pharmacologie , Hypoglycémiants/isolement et purification , Diabète expérimental/traitement médicamenteux , Diabète expérimental/sang , Diabète expérimental/induit chimiquement , Pancréas/effets des médicaments et des substances chimiques , Pancréas/métabolisme , Pancréas/anatomopathologie , Mâle , Rats , Éthanol/composition chimique , Rat Wistar
20.
J Trace Elem Med Biol ; 84: 127450, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38643593

RÉSUMÉ

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.


Sujet(s)
Diabète expérimental , Hémorhéologie , Rat Wistar , Zinc , Animaux , Zinc/sang , Zinc/pharmacologie , Mâle , Diabète expérimental/sang , Diabète expérimental/traitement médicamenteux , Rats , Hémorhéologie/effets des médicaments et des substances chimiques , Glycémie/métabolisme , Viscosité sanguine/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Poids/effets des médicaments et des substances chimiques , Compléments alimentaires
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