Glucose Levels In Diabetic Rats Research Articles

Effects of Insulin and Metformin on Indomethacin-Induced Gastric Injury in Streptozotocin-Induced Diabetic and Non-Diabetic Rats

Diabetes is one of the major health issues globally. Diabetic gastropathy is a well-documented phenomenon. Current treatments for diabetes and its complications have proven to be unsatisfactory. Currently, standard insulin therapy alone is still not the best treatment for type 1 diabetes (T1D). Metformin, besides use in type 2 diabetes (T2D), might be considered for a treatment of T1D. This study analyzed the effects of insulin and metformin on the gastric injury caused by indomethacin in the streptozotocin (STZ)-induced diabetic (T1D) and control non-diabetic rats. STZ (60 mg/kg, i.p.) was administered once 2 weeks before indomethacin (IM, 35 mg/kg, s.c.) in rats. Control non-diabetic rats were injected with STZ vehicle. The development of diabetes was assessed by blood glucose levels, changes in the rats' body weight, and water consumption. Insulin (2 IU/kg, i.p.) and metformin (100 mg/kg, orally) were administered daily, separately to different groups of rats, starting from the 8th day after the administration of STZ, for 7 days. After the last administration of the drugs, the rats were fasted for 22 hours before IM administration. Four hours after IM administration, the rats were decapitated, the stomachs were removed to estimate the erosion area; the adrenal glands and thymus were removed to estimate their weight, and trunk blood was collected to test the corticosterone and glucose levels. During the first week after STZ administration characteristic signs of diabetes developed: increased blood glucose, increased water consumption, and slower body weight gain. A week after daily insulin administration (on the 14th day), the glucose level in diabetic rats was lower compared to the corresponding level on the 7th day (before insulin administration). At the same time, the glucose levels before (day 7) and after administration (day 14) of metformin did not differ significantly. The development of STZ-induced diabetes led to a pronounced worsening of the ulcerogenic effect of IM: the average area of erosions caused by IM was increased significantly compared to that in control non-diabetic rats. Administration of both insulin and metformin for 7 days prevented the ulcer-promoting effect of STZ. In addition, insulin, but not metformin, also had a gastroprotective effect in non-diabetic rats: it reduced the average area of IM-induced erosions. The development of STZ-induced diabetes was accompanied by the manifestation of signs of chronic stress: an increase in plasma corticosterone level, an increase in the relative weight of the adrenal glands, and a decrease in the relative weight of the thymus. Daily administration of insulin for 7 days, but not metformin, resulted in a decrease in corticosterone levels on day 14 in diabetic rats. In conclusion, both insulin and metformin effectively prevented the pronounced ulcer-promoting effect of STZ-induced diabetes on the gastric injury caused by indomethacin in rats. However, only insulin, but not metformin, also exerted gastroprotective effect against IM-induced injury in non-diabetic rats under our experimental conditions. Grant for the creation and development of the world-class scientific center "Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance” and with financial support from the Ministry of Education and Science of the Russian Federation (No 075-15-2022-303 от 21.04.2022.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study

AimThis study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. Materials and methodsEighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. ResultsThe average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. ConclusionMetformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of −17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Development of oral formulation of Lepidium seeds significantly decreases the high blood glucose levels in diabetic rats: in vitro formulation and in vivo antidiabetic performance

Background Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level. Aim The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats’ model in comparison with positive control metformin. Methods Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed. Results Prosolv®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas. Conclusion GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.

INFLUENCE OF FERMENTED MELON SEED (OGIRI) PROTEIN ISOLATE ON POSTPRANDIAL BLOOD GLUCOSE LEVELS IN DIABETIC RATS

ABSTRACT Abstract Introduction Diabetes mellitus is a prevalent endocrine disorder affecting millions worldwide, characterized by chronic hyperglycemia and associated with serious complications. Aim This study aimed to evaluate the anti-diabetic properties of Ogiri Protein Isolate (OPI) derived from fermented melon seeds (Citrullus vulgaris) and its effects on blood glucose levels, lipid profiles, and key organs in alloxan-induced diabetic rats. Methods Forty-two rats were divided into seven groups: positive control, negative control, diabetic group treated with 20% OPI, non-diabetic group treated with 20% OPI, diabetic group treated with 10% OPI, non-diabetic group treated with 10% OPI, and diabetic group treated with 80mg/kg Glibenclamide for 14 days. Fasting serum glucose levels, feed and water intake, weight gain, and plasma HDL-cholesterol and triglyceride levels were measured. Results OPI treatment significantly reduced fasting serum glucose levels in diabetic rats. There was a significant (p&lt;0.05) decrease in feed and water intake in treated groups. Weight gain improved in OPI-treated diabetic rats compared to untreated diabetic rats. Plasma HDL-cholesterol levels increased significantly in all treated groups compared to the control, with the highest levels in non-diabetic and untreated groups. Similar trends were observed in plasma and liver triglycerides. Conclusion The findings suggest that OPI possesses anti-diabetic properties, significantly lowering blood glucose levels and improving lipid profiles in diabetic rats. OPI holds promise as a potential therapeutic agent for diabetes management. Further research is needed to validate these results in human studies. Keywords: Ogiri Protein Isolate (OPI), anti-diabetic, Diabetes mellitus, Postprandial blood glucose and Alloxan.

Multilayer track-etched membrane-based electroosmotic pump for drug delivery.

Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400mmH2 O) of a fundamental pump unit was obtained at 0.8mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7µW. Thus, EOP-3 can run stably over 35h at a pulse current of 0.1mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.

Ethyl Acetate Fractions of Tectona Grandis Crude Extract Modulate Glucose Absorption and Uptake as Well as Antihyperglycemic Potential in Fructose-Streptozotocin-Induced Diabetic Rats.

Type 2 diabetes (T2D) is a global health challenge with increased morbidity and mortality rates yearly. Herbal medicine has provided an alternative approach to treating T2D with limited access to formal healthcare. Tectona grandis is being used traditionally in the treatment of diabetes. The present study investigated the antidiabetic potential of T. grandis leaves in different solvent extractions, and the crude extract that demonstrated the best activity was further fractionated through solvent-solvent partitioning. The ethyl acetate fraction of the ethanol crude extract showed the best antidiabetic activity in inhibiting α-glucosidase, delaying glucose absorption at the small intestine's lumen, and enhancing the muscle's postprandial glucose uptake. The ethyl acetate fraction was further elucidated for its ability to reduce hyperglycemia in diabetic rats. The ethyl acetate fraction significantly reduced high blood glucose levels in diabetic rats with concomitant modulation in stimulated insulin secretions through improved pancreatic β-cell function, insulin sensitivity by increasing liver glycogen content, and reduced elevated levels of liver glucose-6-phosphatase activity. These activities could be attributed to the phytochemical constituents of the plant.

Administrations of Butterfly Pea Flower (Clitoria Ternatea L) Extract Reduce Oxidative Stress and Increase Body Weight of Male Wistar Rats with Diabetes

Background: Asian pigeonwings flower (Clitoria Ternatea L.) is a plant that contains high antioxidants. Numerous research studies have shown that CT flowers can reduce the blood glucose levels of diabetic rats. Lower blood glucose levels can reduce MDA in DM patients. Objectives: This study aimed to analyze the effect of CT on serum malondialdehyde (MDA) levels and body weight of diabetic rats. Methods: Male albino Wistar rats induced by streptozotocin 45 mg/kgBW and nicotinamide 110 mg/kgBW to generate type 2 diabetes. Diabetes rats were randomly divided into three groups: T1 was the control of diabetic rats, T2 was given 300 mg/kgBW extract of CT, and T3 was given 600 mg/kgBW extract of CT for 21 days. Data collected before, during, and after treatment were analyzed using One Way ANOVA and LSD posthoc. Results: The mean of MDA in the T2 and T3 groups decreased on day 14 that was T2 4,67±0,17 µmol/l and T3 3,99±0,30 µmol/l, (p&lt;0,001) and on day 21 also decreased that was T2 4,07±0,14 µmol/l and T3 3,34 ±0,23 µmol/l (p&lt;0,001). While T1 did not experience a significant decrease. The mean of body weight in the T2 and T3 groups increased on day 14 that was T2 187,83±4,67 grams and T3 183,50±4,41 grams (p&lt;0,001), and on day 21, also increased was T2 195,17±3,65 grams, 190,67±4,08 grams (&lt;0,001). In contrast, T1 did not experience a significant increase. Conclusion: Administration of CT flower extract 300 mg/KgBW, and CT flower extract 600 mg/KgBW reduces serum MDA levels of diabetic rats compared to the control of diabetic rats.

PHYTOCHEMICAL STUDY AND ANTIOXIDANT, ANTIBACTERIAL AND ANTIDIABETIC ACTIVITIES OF FLACOURTIA INDICA LEAVES EXTRACTS FROM THE TOGOLESE FLORA

Objective: Faced with the devastating effect of diabetes, the search for new natural antidiabetic molecules is an exploratory avenue. Methods: In this study, the leaves of Flacourtia indica were collected from the Togolese flora, and their antioxidant activity was evaluated using DPPH and FRAP assays, following a phytochemical screening conducted through colorimetric and precipitation reactions. The content of total phenols was determined using Folin-Ciocalteu's reagent and flavonoids by aluminum trichloride. The antibacterial activity of the extracts was evaluated using the method of dilution in agar wells with Muller-Hinton® agar. Additionally, the extracts' antidiabetic effect was evaluated in rats made diabetic by alloxan at a dose of 120 mg/kg. b.w. Results: The results of our work showed the presence of flavonoids, tannins, anthocyanins, and saponins in the extracts. The best polyphenol and flavonoid contents were measured in the hydroethanolic extract and were 186.46±0.308 mg EqAG/g and 464.14±17.043 mgEqQ/g. ES respectively. The hydroethanolic extract has a higher antioxidant power with an IC50 = 110.22 µg/ml. The reducing powers of the ferric ions were 3706±12.124 and 3777±9.238 µmol/ml, respectively for the hydroethanolic and aqueous extracts. The extracts were active against Staphylococcus aureus and are bacteriostatic. The hydroethanolic extract of the leaves of Flacourtia indica significantly reduced (p = 0.0014) blood glucose levels in diabetic rats. Conclusion: This plant can therefore be a potential medicine in the treatment of diabetes.

Phytochemical Screening And Antidiabetic Test Of Ethanol Extract Of Turmeric Leaves (Curcuma domestica Val.) On Decreasing Blood Glucose Of Diabetic Rats

The turmeric plant (Curcuma domestica Val.) is a tropical plant that grows a lot on the Asian continent with is use as a food coloring and fragrance. The use of turmeric leaves by residents is only a cooking ingredient not used in large quantities. Even most of these turmeric leaves are considered waste and have minimal utilization. Turmeric leaf methanol extract can be used to lower blood glucose. Turmeric leaf extract has the potential as a valuable food source of its antioxidant components, such as total phenolic compounds and flavonoids which increase radical scavenging activity. In particular, the water extract of turmeric leaves contains high total phenolic compounds (2.741 ± 0.099 mg GAE/g) and flavonoids (4.776 ± 0.010 mg QCE/g). Diabetes mellitus is a metabolic disorder associated with several chronic complications, such as nephropathy, neuropathy, retinopathy and cardiomyopathy. Part of the turmeric plant leaves is reported to have the ability as an antioxidant. Antioxidant compounds can control blood glucose levels and prevent diabetes complications. This study was conducted to test the ability of turmeric leaf ethanol extract (EEDK) to reduce blood glucose levels in diabetic rats induced by nicotinamide and streptozotocin and to perform phytochemical screening to determine the compounds contained in turmeric leaves so that it becomes an alternative as a diabetes treatment and can prevent damage. or diabetic complications. The results showed that turmeric leaves contained secondary metabolites, namely flavonoids, glycosides, tannins, and triterpenoids/steroids, but there were no alkaloids or saponins. The characterization results show that the sample meets the requirements. Turmeric leaf ethanol extract doses of 400 mg/kg, 200 mg/kg, and 100 mg/kg could reduce the Blood Glucose Level of NA and STZ-induced rats from the fourth day of treatment.

THE EFFECT OF NEEM GUM ON THE REDUCTION IN RAT BLOOD GLUCOSE LEVELS INDUCED BY STREPTOZOTOCIN

Pharmacological therapy for diabetes, which is primarily made up of chemicals, still causes a lot of side effects. The numerous side effects of pharmacological therapy for diabetes have generated innovations in alternative diabetes therapies using ingredients derived from nature. One of the natural ingredients with an anti-hyperglycemia effect is neem gum (NG), or the sap of the neem plant (Azadirachta indica). The aim of this study was to determine the effect of NG on the reduction of blood glucose levels. Moreover, this study had six groups, including a normal control group and groups with doses of 0, 3.75, 7.5, 15, and 30 grams/kgBW. The results showed that NG reduced blood glucose levels in diabetic rats. The paired t-test showed a significant reduction in blood glucose in all groups administered NG except for the dose 3.75 group (P&lt;0.05). The minimum and maximum effective doses of NG were calculated using the quadratic regression test with the equation y = 1.059x2–46.576x+408. With a target blood glucose level of between 80 and 126 mg/dL, the minimum and maximum effective doses of NG were obtained in the range of 12–15 mg/dL. This study concluded that administering NG to diabetic rats can reduce blood glucose levels. Phytochemical studies and research are needed with serial examinations using the effective dose range of neem gum.

Hypoglycemia and anxiolysis mediated by levofloxacin treatment in diabetic rats.

The present study was designed to determine the effect of levofloxacin (LVX) treatment on the blood glucose level, insulin sensitivity, anxiety level, nitrite and MDA level of STZ induced diabetic rats. Wistar rats were used in the present study. The rats were made diabetic by the administration of single dose of STZ (45mg/kg, i.p.) and NAD (50mg/kg, i.p.). The rats with the blood glucose level greater than 200mg/dl were considered as diabetic (confirmed at day-3 of STZ-NAD administration). The non-diabetic rats were considered as control and received saline.Diabetic rats received metformin (50mg/kg, p.o.) and LVX (20, 25, 30 and 35mg/kg, i.p.) daily for 14 days (starting from the day at which STZ was injected). Following administration on 14th day,the blood sample was collected and the rats were subjected to behavioral assays for the determination of locomotor activity and anxiety level. Plasma was separated and used for the estimation ofnitrite and malondialdehyde (MDA)level. On 15th day OGTT was performed in the overnight fasted rats for the assessment of insulin sensitivity. The results obtained suggested that the administration of STZ-NAD induced the hyperglycemia at day-3 of administration. Diabetic rats displayed the significant increase in blood glucose, anxiety related behavior, MDA level while significant decrease in the insulin sensitivity and plasma nitrite level. Daily administration of metformin to the diabetic rats decreased the blood glucose level, increased the time spent at the center of open field, reversed the anxiety related behavior in LDT and EPM, did not affect the plasma nitrite level, decreased the plasma MDA level, decreased the fasting glucose level and AUC in OGTT assay. LVX (30 and 35mg/kg) treatment significantly decreased the blood glucose level of diabetic rats. LVX (20, 25 and 30mg/kg) treatment significantly decreased the number of square crossing while LVX (20, 25, 30 and 35) treatment significantly increased the time spent at the center of the field by the diabetic rats. LVX (20 and 35mg/kg) treatment significantly reversed the STZ induced anxiety in LDT while LVX (20, 30 and 35mg/kg) treatment significantly reversed the STZ induced anxiety in EPM test. LVX (20, 25 and 35mg/kg) treatment significantly increased the plasma nitrite level and LVX (20-35mg/kg) treatment significantly decreased the MDA level of diabetic rats. Further only LVX (35mg/kg) treatment significantly decreased the fasting glucose level and increased the AUC of diabetic rats. In conclusion, STZ-NAD administration increased the blood glucose level, anxiety related behavior, decreased the plasma nitrite and increased the MDA level. LVX administration potentiated the diabetogenic effects of STZ-NAD in rats. Daily administration of LVX decreased the blood glucose level of diabetic rats. LVX administration alleviated the STZ induced anxiety in OFT, LDT and EPM test. LVX administration increased the plasma nitrite level and decreased the lipid peroxidation in diabetic rats. The online version contains supplementary material available at 10.1007/s40200-023-01234-0.

Effect of Ethanolic leaf extract of Elaeocarpus tectorius (Lour.) Poir. on Retinal Oxidative Stress in Streptozotocin-nicotinamide Induced Diabetic rats

Oxidative stress plays a crucial role in the pathogenesis of diabetic retinopathy and causes loss of vision. Elaeocarpus tectorius (Lour.) Poir. is a tree species that bears edible fruits and is traditionally used to treat diabetes. The study is aimed to investigate the ameliorative effect of ethanolic leaf extract of E. tectorius on retinal oxidative stress and aldose reductase levels in STZ-NIC-induced diabetic rats. The leaf extract was orally administered to diabetic rats once a day for about 28 days at doses of 200 and 400 mg/kg b.w. Fasting blood glucose levels were determined at regular intervals during the treatment period and retinal superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, lipid peroxidation levels and aldose reductase activity were assessed at the end of the experiment. Oral administration of E. tectorius leaf extract caused a significant decrease in the fasting blood glucose levels of diabetic rats. The extract also improved the retinal antioxidant status by increasing the levels of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione. The rate of lipid peroxidation was lowered in diabetic rats as a result of treatment with the leaf extract. The diabetic rats treated with the leaf extracts also had lower retinal aldose reductase activity when compared to the untreated diabetic rats. This study suggests that Elaeocarpus tectorius leaf extracts exhibit protective effects and improve the antioxidant status of the retina under diabetic conditions helping in the prevention and management of diabetic retinopathy.

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain.

The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall-Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain.

Fabrication, optimization, and eco-friendly micellar HPLC determination of Alogliptin/Dapagliflozin pullulan-based sublingual films for therapeutic efficacy improvement in diabetic rats

The aim of this study was to prepare and statistically optimize a pullulan-based sublingual film containing Alogliptin/Dapagliflozin (ALO/DAPA) mixture, by solvent casting technique to provide a promising remedy for type 2 diabetes. Sublingual films were optimized by employing a central composite design created by the Design Expert® software. The optimized formula was further determined using a novel eco-friendly micellar HPLC method. The separation was carried out on a Kinetex C18 column (100 mm × 4.6 mm i. d, 2.6-μm particle size) with isocratic elution at a flow rate of 1 mL/min and UV detection at 230 nm. The micellar aqueous mobile phase used for the separation was composed of 50 mM sodium dodecyl sulfate, 15% pentanol, and 50 mM sodium dihydrogen phosphate (pH 3.5). The antidiabetic effects of ALO/DAPA sublingual films on the blood glucose levels of diabetic rats and their effect on the pancreas and kidney histopathology were studied. The developed method was accurate, and precise and can be used for the simultaneous estimation of both drugs without any interference in their sublingual films. Moreover, the greenness of the suggested method has been evaluated by different tools; analytical Eco-scale and the Green Analytical procedure Index, which shows that it has the least environmental impact. The ALO/DAPA sublingual film optimal formula showed mechanical strength of 2.69 ± 0.23 N/mm2, folding endurance of 69 ± 2.13 times, and in-vitro disintegration of 71.7 ± 1.23 s indicating acceptable formulation and mechanical parameters. A significant improvement in glycemic control where the blood glucose level was normalized (137 ± 23) after 4 h compared to the commercial drugs (247 ± 27.4) at p < 0.05 was attained. Additionally, islets of Langerhans appeared apparently normal with average size and intact cells with the improvement of the histopathological examination of renal tissues. This study introduced a successful and promising sublingual film as a drug delivery system of ALO/DAPA mixture for the treatment of type 2 diabetes.

MP27-10 CRISPRA-ENGINEERED ADIPOSE-DERIVED STEM CELLS IMPROVE ERECTILE DYSFUNCTION IN DIABETIC RATS

You have accessJournal of UrologyCME1 Apr 2023MP27-10 CRISPRA-ENGINEERED ADIPOSE-DERIVED STEM CELLS IMPROVE ERECTILE DYSFUNCTION IN DIABETIC RATS Wenchao Xu, Hao Li, Taotao Sun, Jiaxin Wang, Tao Wang, and Jihong Liu Wenchao XuWenchao Xu More articles by this author , Hao LiHao Li More articles by this author , Taotao SunTaotao Sun More articles by this author , Jiaxin WangJiaxin Wang More articles by this author , Tao WangTao Wang More articles by this author , and Jihong LiuJihong Liu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the high incidence of diabetes mellitus (DM) and poor response to phosphodiesterase type 5 inhibitor in DM-induced erectile dysfunction (DMED) patients, new therapeutic strategies for DMED are needed. Adipose-derived stem cells (ADSCs) transplantation is considered a promising treatment for DMED but is limited by poor survival and efficacy after transplantation. This study explored the therapeutic effect of CRISPRa-engineered ADSCs overexpressing GPX4 (GPX4-ADSCs) on erectile function in diabetic rats. METHODS: Thirty-two SD rats were randomly divided into four groups: the control, DMED, ADSCs, GPX4-ADSCs groups. Among them, the control group rats were non-diabetic rats, and the latter four groups were all diabetic ED rats of the same age. CRISPRa system was used to overexpress GPX4 in ADSCs. The GPX4-ADSCs group was treated with intracavernous injections of GPX4-ADSCs, while the ADSCs group was treated with ADSCs. Four weeks after transplantation, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured by electrical stimulation of cavernous nerve, and penile tissue was collected for subsequent testing. RESULTS: ADSCs and GPX4-ADSCs transplantation did not affect the weight or the glucose levels of diabetic rats. Although both the ADSCs group and the GPX4-ADSCs group improved erectile function in diabetic rats, the GPX4-ADSCs group had better improvement than the ADSCs group. In the DMED group, oxidative levels in the corpus cavernosum increased, PI3K/AKT/eNOS signal expression was down-regulated, Caspase3 activity was enhanced, and TGFβ1-Smad2/3-Collagen IV pathway was upregulated, showing obvious oxidative stress, apoptosis and fibrosis. ADSCs and GPX4-ADSCs can reverse these changes caused by diabetes to some extent, and GPX4-ADSCs are more effective than ADSCs. CONCLUSIONS: The CRISPRa-engineered ADSCs overexpressing GPX4 had stronger efficacy in improving erectile function than ADSCs, and the mechanism may involve reducing oxidative stress, apoptosis, and fibrosis, which provides a new strategy for the treatment of DMED. Source of Funding: This research was funded by grants from the National Natural Science Foundation of China (No. 82001536 and No.81873831) and the Fundamental Research Funds for the Central Universities (HUST: YCJJ202201021) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e366 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wenchao Xu More articles by this author Hao Li More articles by this author Taotao Sun More articles by this author Jiaxin Wang More articles by this author Tao Wang More articles by this author Jihong Liu More articles by this author Expand All Advertisement PDF downloadLoading ...

Wearable, Sensing-Controlled, Ultrasound-Based Microneedle Smart System for Diabetes Management.

An intelligent closed-loop system that senses glucose and automatically delivers insulin can provide enhanced glycemic control for diabetes management. Here, we report for the first time on the development of a wearable, sensing-controlled, ultrasound-based closed-loop microneedle smart system for diabetes management. Polylactic acid (PLA) hollow microneedles were fabricated by soft lithography that can maintain excellent mechanical strength and stability in biofluids, followed by the deposition of sensing electrodes on the outer layer. An ultrasonic insulin pump was constructed by integrating a lead zirconate titanate piezoelectric (PZT) ring and a biocompatible stainless-steel sheet with hundreds of tapered holes on top of the inner layer of the microneedles. Both the sensor and the pump were powered and controlled by a printed circuit board (PCB). When the sensing device detects interstitial glucose levels above normal, the closed-loop control algorithm triggers the ultrasonic pump to deliver insulin into the interstitial fluid through the microneedle hollow channels of the PLA microneedles. The ultrasound from the pump can cause the vaporization of insulin in the subcutaneous tissue fluid, accelerate the diffusion rate, and improve the efficiency of insulin treatment and utilization. The system has successfully demonstrated effective control of glucose levels in diabetic rats. The glucose sensor showed a high sensitivity of 0.212 μA/mM at 0-28 mM with a detection limit of 14 μM, and the mean absolute relative difference (MARD) was 9.96% with an average error of 1.6 mM. The flow rate of the ultrasonic pump was 120 μL/min, and the glucose-lowering rate was 4 mM/h. This work may open a new paradigm for the development of intelligent systems for diabetes management, as well as a wide range of practical applications in diabetes patients.

Transdermal Delivery of Insulin Using Combination of Iontophoresis and Deep Eutectic Solvents as Chemical Penetration Enhancers: In Vitro and in Vivo Evaluations

A serious challenge in transdermal iontophoresis (IP) delivery of insulin (INS) is the low permeability of the drug across the skin. In this paper, we introduced deep eutectic solvent (DESs) as novel chemical penetration enhancers (CPEs) for transdermal IP of INS across rat skin, both in vitro and in vivo. Three different DESs based on choline chloride (ChCl), namely, ChCl/UR (ChCl and urea), ChCl/GLY (ChCl and glycerol), and ChCl/EG (ChCl and ethylene glycol) in the 1:2 molar ratios have been prepared. To evaluate the capability of studied DESs as CPEs for IP delivery of INS, the rat skin sample was treated with each DES. The effects of different experimental parameters (current density, formulation pH, INS concentration, NaCl concentration, and treatment time) on the in vitro transdermal iontophoretic delivery of INS were investigated. The in vitro permeation studies exhibited that INS was easily delivered employing ChCl/EG, and ChCl/GLY treatments, compared with ChCl/UR: the cumulative amount of permeated INS at the end of the experiment (Q24h) was found to be 131.0, 89.4, and 29.6 µg cm−2 in the presence of ChCl/EG, ChCl/GLY, and ChCl/UR, respectively. The differences in Q24h values of INS are due to the different capabilities of the studied DESs to treat the epidermis layer of skin. In vivo experiments revealed that the blood glucose level in diabetic rats could be decreased using ChCl/EG, and ChCl/GLY as novel CPEs in the IP delivery of INS. The presented work will open new doors towards searching for novel CPEs in the development of transdermal IP of INS.

Unlocking the therapeutic potential of Garcinia cowa Rox. in diabetes management

Garcinia cowa Rox. is a tropical fruit traditionally used in various parts of Asia for medicinal purposes. Recent research has indicated that it may have potential as an antidiabetic drug. Studies have shown that the extract from the fruit of G. cowa can lower blood glucose levels in diabetic rats. This effect is believed to be due to various bioactive compounds, including flavonoids and xanthones, which have demonstrated antidiabetic properties. In addition, fruit extract has also been found to improve lipid metabolism, often disrupted in individuals with diabetes. The extract has been shown to reduce levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol while increasing high-density lipoprotein cholesterol levels. Further studies are needed to explore the full potential of G. cowa as an antidiabetic drug, including clinical trials in humans. However, these initial findings suggest that this tropical fruit is a promising natural and effective treatment option for individuals with diabetes.

Dietary administration with hydrolyzed silk sericin improves the intestinal health of diabetic rats.

Type II diabetes (T2D) is a global epidemic disease with an increased incidence and prevalence. Gut microbiota plays an important role in controlling T2D development. Dietary administration of prebiotics, probiotics, and drugs, including metformin, showed the regulatory impact on the change of gut microbiota, which is associated with the improvement of glucose tolerance. In this study, silk sericin was manufactured into hydrolyzed sericin peptide (HSP) powders as a dietary additive to investigate the effect on the gut microbiota of T2D model rats. The results indicated that the HSP-augmented dietary administration lowers the fast glucose level of diabetic rats, and HSP augmentation induces a change in the gut microbiota composition of T2D model rats toward the normal rats. Some key taxa, including Lactobacillus gasseri, were suggested to be involved in controlling T2D development. This finding provides new insight into developing sericin as functional food or therapeutic prebiotics against T2D in clinical practice.