EGb761, a Ginkgo Biloba Extract, Is Effective Against Atherosclerosis In Vitro, and in a Rat Model of Type 2 Diabetes

To investigate the effects of Ginkgo biloba extract (GbE) on the activities of energy metabolism enzymes and contraction capacity of diaphragm from type 2 diabetic rats. Forty SD mile rats were randomly divided into normal control group (n=10) and model group (n=30). Type 2 diabetes models were induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting 25mg/kg streptozotocin. 20 successful models were rearranged to two groups: diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8mg·kg-1·d-1 of GbE were respectively intraperitoneal injected, once a day continuously for 8 weeks. Then diaphragm contractility was assessed using Peak twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the varieties of diaphragm ultrastructure were observed. Compared with control group, Pt, P0 and FI in diabetic group decreased significantly (P < 0.01); the activity of CCO, LDH and SDH in the tissues was obviously reduced than those in control group (P < 0.01). The ultrastructure in diabetic group under electron microscope indicated that diaphragm mitochondrions swelled and degenerated. The above changes were inhibited by GbE. GbE can enhance contraction capacity of diaphragm from type 2 diabetic rats by increasing the aerobic oxidation capacity, glycolytic capacity and the function of respiratory chain.

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Skeletal muscle energetics are compromised only during high-intensity contractions in the Goto-Kakizaki rat model of type 2 diabetes

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00127.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. R356-R368 ◽

Cited By ~ 3

Author(s):

Matthew T. Lewis ◽

Jonathan D. Kasper ◽

Jason N. Bazil ◽

Jefferson C. Frisbee ◽

Robert W. Wiseman

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Rat Model ◽

Mitochondrial Function ◽

The United States ◽

Gk Rat ◽

Muscle Energetics ◽

Atp Production

Type 2 diabetes (T2D) presents with hyperglycemia and insulin resistance, affecting over 30 million people in the United States alone. Previous work has hypothesized that mitochondria are dysfunctional in T2D and results in both reduced ATP production and glucose disposal. However, a direct link between mitochondrial function and T2D has not been determined. In the current study, the Goto-Kakizaki (GK) rat model of T2D was used to quantify mitochondrial function in vitro and in vivo over a broad range of contraction-induced metabolic workloads. During high-frequency sciatic nerve stimulation, hindlimb muscle contractions at 2- and 4-Hz intensities, the GK rat failed to maintain similar bioenergetic steady states to Wistar control (WC) rats measured by phosphorus magnetic resonance spectroscopy, despite similar force production. Differences were not due to changes in mitochondrial content in red (RG) or white gastrocnemius (WG) muscles (cytochrome c oxidase, RG: 22.2 ± 1.6 vs. 23.3 ± 1.7 U/g wet wt; WG: 10.8 ± 1.1 vs. 12.1 ± 0.9 U/g wet wt; GK vs. WC, respectively). Mitochondria isolated from muscles of GK and WC rats also showed no difference in mitochondrial ATP production capacity in vitro, measured by high-resolution respirometry. At lower intensities (0.25–1 Hz) there were no detectable differences between GK and WC rats in sustained energy balance. There were similar phosphocreatine concentrations during steady-state contraction and postcontractile recovery (τ = 72 ± 6 s GK versus 71 ± 2 s WC). Taken together, these results suggest that deficiencies in skeletal muscle energetics seen at higher intensities are not due to mitochondrial dysfunction in the GK rat.

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Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

International Journal of Molecular Sciences ◽

10.3390/ijms21145045 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5045

Author(s):

Istvan Kovanecz ◽

Robert Gelfand ◽

Sheila Sharifzad ◽

Alec Ohanian ◽

William DeCastro ◽

...

Keyword(s):

Type 2 Diabetes ◽

Urinary Incontinence ◽

Stem Cell ◽

Stress Urinary Incontinence ◽

Rat Model ◽

Male Rats ◽

Female Stress Urinary Incontinence ◽

Female Rat

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.

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Improved haemorrheological properties by Ginkgo biloba extract (Egb 761) in type 2 diabetes mellitus complicated with retinopathy

Clinical Nutrition ◽

10.1016/j.clnu.2003.10.010 ◽

2004 ◽

Vol 23 (4) ◽

pp. 615-621 ◽

Cited By ~ 44

Author(s):

Shih-Yi Huang ◽

Chii Jeng ◽

Shou-Chuan Kao ◽

Joseth Jy-Hau Yu ◽

Der-Zen Liu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Ginkgo Biloba ◽

Ginkgo Biloba Extract ◽

Egb 761

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EARLY CONSUMPTION OF HIBISCUS SABDARIFA ATTENUATES THE SEVERITY OF TYPE 2 DIABETES IN A WISTAR RAT MODEL

International Journal of Advanced Research ◽

10.21474/ijar01/13808 ◽

2021 ◽

Vol 9 (11) ◽

pp. 815-823

Author(s):

Maxime Machioud Sangare ◽

◽

Abdoulaye Issotina Zibrila ◽

Felix Fanou Guinnin ◽

Mabou Herman Kpomalegni Guehou ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Rat Model ◽

Crude Extract ◽

Wistar Rat ◽

Scavenging Activity ◽

Blood Biochemical ◽

Elevated Glucose

Diabetes constitute a serious challenge for many health system and families due to the cost of its care. Alternatively, traditional plants offer a huge potential for health care. Thus, many plants have been used in form beverage including the use of Hibiscus sabdarifa (HS) as tea. Recent data suggested the beneficial effect of HS cardiometabolic diseases models. In this study, we evaluated the preventive and curative effects of crude extract of HS in a type 2 diabetes rat model. Through in vitro complexion and/ or precipitation reactions, we qualitatively assessed the phytochemical composition of the crude extract of HS for different groups of secondary metabolites. The antiradical scavenging activity was assessed through hydroxyl radical test. Type 2 diabetes was induced by high fat diet (HFD) and single dose streptozotocine (STZ) injection. Body weight change and blood biochemical analysis were carried out. Data were statistically analyzed. HS contains different phytochemical polyphenolic compounds such as tanins and flavonoids and presented an interesting antiradical scavenging activity. Early intake from experimental day (ED1) of crude extract of HS significantly prevented gain in body weight (P < 0.05), reduced T2D induced elevated glucose (P < 0.01) and lipids (P < 0.01) and has better outcome as compared to late intake (from ED14). These findings confirm and supports the use of HS as tea and may offer protective effect to consumers by regulating blood sugar and lipid profile.

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Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms20164044 ◽

2019 ◽

Vol 20 (16) ◽

pp. 4044 ◽

Cited By ~ 2

Author(s):

Istvan Kovanecz ◽

Robert Gelfand ◽

Guiting Lin ◽

Sheila Sharifzad ◽

Alec Ohanian ◽

...

Keyword(s):

Type 2 Diabetes ◽

Stem Cells ◽

Urinary Incontinence ◽

Stem Cell ◽

Stress Urinary Incontinence ◽

Rat Model ◽

Repair Capacity

Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC). This was mimicked in vitro by treatment of MDSC with dyslipidemic serum or lipid factors. The current study aimed to predict whether these changes also occur in stem cells from female 12 weeks old T2D/O rats, a model of FSUI. MDSCs from T2D/O (ZF4-SC) and normal female rats (ZL4-SC) were treated in vitro with either dyslipidemic serum (ZFS) from late T2D/O 24 weeks old female Zucker fatty (ZF) rats, or normal serum (ZLS) from 24 weeks old female Zucker lean (ZL) rats, for 4 days and subjected to assays for fat deposition, apoptosis, scratch closing, myostatin, interleukin-6, and miR-GTS. The dyslipidemic ZFS affected both female stem cells more severely than in the male MDSC, with some gender-specific differences in miR-GTS. The changes in miR-GTS and myostatin/interleukin-6 balance may predict in vivo noxious effects of the T2D/O milieu that might impair autograft stem cell (SC) therapy for FSUI, but this requires future studies.

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Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model

Scientific Reports ◽

10.1038/s41598-019-53996-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Bibhu Prasad Panda ◽

Rachna Krishnamoorthy ◽

Subrat Kumar Bhattamisra ◽

Naveen Kumar Hawala Shivashekaregowda ◽

Low Bin Seng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Drug Delivery ◽

Rat Model ◽

Second Generation ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Poloxamer 188

AbstractDrug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (−18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.

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1045: Pioglitazone Ameliorates Penile Corpora Veno-Occlusive Dysfunction (CVOD) in a Rat Model of Type 2 Diabetes

The Journal of Urology ◽

10.1016/s0022-5347(18)35201-7 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 283-284

Author(s):

Istvan Kovanecz ◽

Monica G. Ferrini ◽

Hugo H. Davila ◽

Jacob Rajfer ◽

Nestor F. Gonzalez-Cadavid

Keyword(s):

Type 2 Diabetes ◽

Rat Model

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Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

Medicinal Chemistry ◽

10.2174/1573406416666200826101205 ◽

2020 ◽

Vol 16 ◽

Author(s):

Marjan Mollazadeh ◽

Maryam Mohammadi-Khanaposhtani ◽

Yousef Valizadeh ◽

Afsaneh Zonouzi ◽

Mohammad Ali Faramarzi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kinetic Study ◽

Active Site ◽

Docking Study ◽

Secondary Amines ◽

Molecular Docking Study ◽

Glucosidase Inhibitors ◽

Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

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Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽

10.3390/cells10020268 ◽

2021 ◽

Vol 10 (2) ◽

pp. 268

Author(s):

Jonathan Ribot ◽

Cyprien Denoeud ◽

Guilhem Frescaline ◽

Rebecca Landon ◽

Hervé Petite ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bone Marrow ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Therapeutic Modality ◽

Multipotent Stromal Cells ◽

Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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