scholarly journals 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

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.

scholarly journals 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

2019 ◽  
Vol 20 (16) ◽  
pp. 4044 ◽  
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.

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

2019 ◽  
Vol 317 (2) ◽  
pp. R356-R368 ◽  
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.

Therapeutic Potential of Adipose-derived Stem Cell-based Microtissues in a Rat Model of Stress Urinary Incontinence

Urology ◽  
2016 ◽  
Vol 97 ◽  
pp. 277.e1-277.e7 ◽  
Author(s):  
Meng Li ◽  
Guangyong Li ◽  
Hongen Lei ◽  
Ruili Guan ◽  
Bicheng Yang ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Stem Cell ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cell

scholarly journals Local Application of Semaphorin 3A Combined with Adipose-Derived Stem Cell Sheet and Anorganic Bovine Bone Granules Enhances Bone Regeneration in Type 2 Diabetes Mellitus Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaoru Xu ◽  
Kaixiu Fang ◽  
Lifeng Wang ◽  
Xiangwei Liu ◽  
Yuchao Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Stem Cell ◽  
Bone Healing ◽  
Cell Sheet ◽  
Semaphorin 3A ◽  
Adipose Derived Stem Cell

Bone tissue regeneration is considered to be the optimal solution for bone loss. However, diabetic patients have a greater risk of poor bone healing or bone grafting failure than nondiabetics. The purpose of this study was to investigate the influence of the complexes of an adipose-derived stem cell sheet (ASC sheet) and Bio-Oss® bone granules on bone healing in type 2 diabetes mellitus (T2DM) rats with the addition of semaphorin 3A (Sema3A). The rat ASC sheets showed stronger osteogenic ability than ASCs in vitro, as indicated by the extracellular matrix mineralization and the expression of osteogenesis-related genes at mRNA level. An ASC sheet combined with Bio-Oss® bone granules promoted bone formation in T2DM rats as indicated by microcomputed tomography (micro-CT) and histological analysis. In addition, Sema3A promoted the osteogenic differentiation of ASC sheets in vitro and local injection of Sema3A promoted T2DM rats’ calvarial bone regeneration based on ASC sheet and Bio-Oss® bone granule complex treatment. In conclusion, the local injection of Sema3A and the complexes of ASC sheet and Bio-Oss® bone granules could promote osseous healing and are potentially useful to improve bone healing for T2DM patients.

scholarly journals Characterization of Novel Nonobese Type 2 Diabetes Rat Model with Enlarged Kidneys

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ayaka Domon ◽  
Kentaro Katayama ◽  
Yuki Tochigi ◽  
Hiroetsu Suzuki
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Inflammatory Cells ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Oral Glucose ◽  
Renal Tubules ◽  
Age Related

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of β cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying β cell loss and identifying genetic factors protective against DN.

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

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20301 ◽  
Author(s):  
Soo Lim ◽  
Ji Won Yoon ◽  
Seon Mee Kang ◽  
Sung Hee Choi ◽  
Bong Jun Cho ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract

202 MUSCLE DERIVED STEM CELL/ALGINATE/PCL/INJECTION THERAPY IN RAT MODEL OF STRESS URINARY INCONTINENCE

2007 ◽  
Vol 6 (2) ◽  
pp. 73
Author(s):  
J.S. Koh ◽  
H.S. Kim ◽  
J.C. Kim ◽  
D.H. Lee ◽  
H.N. Lee ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
Stem Cell ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Injection Therapy

scholarly journals Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

2018 ◽  
Vol 52 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Titin Andri Wihastuti ◽  
Teuku Heriansyah ◽  
Hanifa Hanifa ◽  
Sri Andarini ◽  
Zuhrotus Sholichah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Foam Cells ◽  
Male Rats ◽  
Sprague Dawley ◽  
Early Stages ◽  
Sprague Dawley Rat

AbstractObjective. Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.Methods. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.Results. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.Conclusion. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

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

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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