meta-Iodobenzylguanidine uptake in the hypertensive–diabetic rat heart: a marker for myocardial dysfunction?

1994 ◽  
Vol 72 (10) ◽  
pp. 1162-1167 ◽  
Author(s):  
Lynda M. Herman ◽  
Soter Dai ◽  
Neil G. Hartman ◽  
John H. McNeill

The purpose of this study was to investigate the cardiac adrenergic neuronal changes induced by diabetes and hypertension by using an analogue of norepinephrine, meta-iodobenzylguanidine (MIBG), and to compare these changes with the contractile state of ventricular papillary muscle. The tissue concentration of norepinephrine in the cardiac apex was also measured for direct comparison with [123I]MIBG uptake. One week following the induction of diabetes by streptozotocin injection (55 mg/kg, i.v.), male Sprague – Dawley rats were given subcutaneous injections of a hypertension-inducing agent, deoxycorticosterone acetate (DOC A, 25 mg/kg), or DOCA vehicle twice weekly for 3, 6, 9, or 12 weeks. At the end of each time point, the animals were injected intravenously (15 mCi/mg; 1 Ci = 37 GBq) with [123I]MIBG. The results showed a progressive decrease in MIBG uptake into the hearts of diabetic, hypertensive, and diabetic–hypertensive rats during the 12-week observation period, compared with the control group. However, length–tension papillary muscle studies at 12 weeks indicated that only the diabetic group had a diminished performance compared with control. Furthermore, an inverse relationship was observed between MIBG uptake and norepinephrine levels in the cardiac apex of the diabetic and diabetic–hypertensive groups. Therefore, we concluded that either MIBG does not provide an accurate indication of adrenergic integrity or that there is no relationship between sympathetic activity and myocardial function at the time points measured. MIBG did not prove to be a useful marker for myocardial dysfunction in diabetic rats.Key words: diabetes, deoxycorticosterone acetate hypertension, meta-iodobenzylguanidine, adrenergic function, heart.

Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.


PRAXIS ◽  
2019 ◽  
Vol 1 (2) ◽  
pp. 180
Author(s):  
Bernadia Branitamahisi

Abstract: Type 2 diabetes mellitus is the highest prevalence among diabetes types, but there is no treatment that overcome obstacle in the process of surgery, rejection reactions, and increased complications that occur. The aim of this study was to investigate the insulin sensitivity improvement by Mesenchymal Stem Cell-Conditioned Medium(MSC-CM) through increased IRS-1 tyrosine phosphorylation (IRS-1tyr612) on the type 2 diabetic rat with and without treatment. This experimental study is purely laboratory Posttest Control Group using male Sprague Dawley rat, 7 weeks old and 150-200gram weight. Rat is divided into 3 research groups, K(-): normal control; K(+): diabetic control; P:treatment, type 2 DM rat+MSC-CM 0,1ml/200gBW ip. Giving MSC-CM is done every 3 days 10 times. On day 30 after therapy, an IRS-1tyr612 expression analysis was performed with skeletal muscle immunohistochemistry (IHC). Data analysis was performed by Kruskal-Wallis and Independent Sample T-test at 95% significance. Percentage of positive score of IRS-1tyr612 expression K(-)(75%)> P(62,5%)> K(+)(12,5%). Average expression of IRS-1tyr612 P(45,46±9,15)> K(-)(44,41±4,61)> K(+)(21,29±3,49) with significant difference of K(-)-K(+) and P-K(+). Giving MSC-CM may increase the expression of IRS-1tyr612 on type 2 diabetic animal model rat. Keywords: MSC-CM, insulin sensitivity, IRS-1tyr612, type 2 DM Abstrak: Diabetes melitus tipe 2 merupakan tipe diabetes dengan prevalensi tertinggi, namun belum ada pengobatan yang dapat mengatasi hambatan dalam proses operasi, reaksi rejeksi, dan banyaknya komplikasi yang terjadi. Penelitian ini bertujuan untuk mengetahui perbaikan sensitivitas insulin oleh Media Terkondisi Sel Punca Mesensimal (MT-SPM) melalui peningkatan fosforilasi tirosin 612 IRS-1(IRS-1tyr612) pada tikus model DM tipe 2 dengan dan tanpa terapi. Penelitian ini eksperimental murni laboratorium Posttest Control Group menggunakan hewan uji tikus Sprague Dawley jantan usia 7 minggu dan berat badan 150-200gram. Tikus dibagi menjadi 3 kelompok penelitian, yaitu K(-): kontrol normal; K(+): kontrol diabetik; P: perlakuan, tikus DM tipe 2 + MT-SPM 0,1ml/200g bb ip. Pemberian MT-SPM dilakukan setiap 3 hari sebanyak 10 kali. Pada hari ke-30 setelah terapi, dilakukan analisis ekspresi IRS-1tyr612 dengan IHC otot skelet. Analisis data dilakukan dengan Independent Sample T-test dan Kruskal Wallis pada signifikansi 95%. Prosentase skor positif ekspresi IRS-1tyr612 K(-)(75%) > P(62,5%) > K(+)(12,5%). Rerata ekspresi IRS-1tyr612 P(45,46±9,15) > K(-)(44,41±4,61) > K(+)(21,29±3,49) dengan perbedaan yang bermakna secara statistik pada K(-)–K(+) dan P–K(+). Pemberian MTSPM dapat meningkatkan ekspresi IRS-1tyr612 pada tikus model DM tipe 2. Kata kunci: MT-SPM, sensitivitas insulin, IRS-1tyr612,DM tipe 2


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Giuseppe Ristagno ◽  
Tong Wang ◽  
Min-Shan Tsai ◽  
Shijie Sun ◽  
Wanchun Tang ◽  
...  

Introduction. High energy defibrillation is recognized to increase postresuscitation myocardial dysfunction. We examined the effects of defibrillation energies on contractility and intracellular Ca 2+ dynamics at the single cardiomyocyte level. Hypothesis. Increasing the defibrillation energy would produce correspondent reduction in myocyte contractility and impairment of intracellular Ca 2+ dynamics. Methods. Ventricular cardiomyocytes, obtained from adult Sprague-Dawley rat hearts, were loaded with Fura-2/AM. The myocytes were then placed in a chamber mounted on an inverted microscope and superfused with a buffer solution at 37 °C. The cells were field stimulated to contract at 0.5 Hz with a field stimulator (IonOptix Corporation, Milton, MA). Mechanical properties were assessed using a video-based edge-detection system (IonOptix Corporation, Milton, MA) and expressed as cell shortening percentage. Intracellular Ca 2+ dynamics were evaluated with a dual-excitation fluorescence photomultiplier system (IonOptix Myocam System) and inferred from the ratio of the fluorescence intensity at the two different wavelengths. Myocytes were randomized into 4 groups of 10 cells each, to receive: a single 0.5 Joule biphasic shock; a single 1 Joule biphasic shock; a single 2 Joule biphasic shock; and a control group without shock. The myocytes were paced for additional 4 min after the shock. Results. A 0.5 Joule shock did not have effects on cardiomyocyte contractility and intracellular Ca 2+ dynamics. Higher energy shock, i.e. 1 or 2 Joule, significantly impaired cardiomyocyte contractility and intracellular Ca 2+ dynamics (p < 0.01). These adverse effects were greater when higher energy was employed (p < 0.01). Table Conclusions. Higher defibrillation energy significantly impairs myocyte contractility. Reductions in cardiomyocyte shortening and intacellular Ca 2+ dynamics abnormalities were greater when higher energy shock was employed. Results


Author(s):  
Holifa Saheera Asmara ◽  
Zubaidi Abdul Latif ◽  
Ahmed Ghazi Faisal ◽  
Mainul Haque

  Objective: The aim of the current study is to compare the difference of Tri-E® and ATF potentials in reducing diabetic adverse event due to hyperglycemia that might cause the DNA damage and cognitive impairment indirectly.Methods: Diabetic model sample from Sprague Dawley was developed by combination of twice low-dose streptozotocin injection and high fat diet. The diabetic rat model was treated with Tri-E® and ATF in different groups, control group were provided. The DNA was collected from the whole blood and DNA damage was measured using the comet assay method. While cognitive status was measured using Morris water-maze method.Result: Reduction of the DNA damage and improvement of cognitive function were observed in both ATF and Tri-E® supplementations that elevated in diabetic. However, the DNA damage reduction by Tri-E® was one-fold higher compared to ATF supplementation.Conclusion: This study provided data that Tri-E® has superior potential than ATF as a preventative agent to DNA damage and cognitive impairment in diabetes indirectly.


Biomedika ◽  
2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Ira Cinta Lestari

ABSTRAKDaun mahkota dewa (Phaleria macrocarpa) diketahui memiliki efek anti hiperglikemik dengan menghambat aktivitas enzim pencerna karbohidrat a-glucosidase, namun efeknya pada kondisi diabetes belum diketahui. Penelitian ini bertujuan untuk mengetahui efek antidiabetik ekstrak etanol daun mahkota dewa (EEDMD) terhadap berat badan dan kadar glukosa darah tikus model diabetes. Studi eksperimental dengan rancangan post test only control group design dilakukan terhadap subjek 45 ekor tikus Sprague Dawley. Subjek dikelompokkan dalam kontrol normal, kontrol diabetes diberi pelarut dan diabetes diberi 7mg/200g, 14mg/200g, and 28mg/200g  EEDMD secara peroral, sekali sehari selama 3, 14 dan 25 hari. Model tikus diabetes dibuat dengan injeksi streptozotosin dan nicotinamide. Hasil analisa statistik berat badan dan kadar glukosa puasa antar kelompok terdapat perbedaan yang signifikan. Sehingga kesimpulan penelitian ini adalah pemberian EEDMD memiliki efek antidiabetik pada tikus diabetes yang dinduksi stretozotosin.Kata kunci: Diabetes Mellitus, Phaleria Macrocarpa, Ekstrak Etanol, Streptozotosin, Antidiabetik ABSTRACTPhaleria macrocarpa leaf has been known to have anti-hyperglycemic effects by inhibiting the activity of a-glucosidase carbohydrates digestive enzyme, but the systemic effect on diabetic condition is unknown yet. This study was conducted to investigate the antidiabetic effect of ethanolic extract of Phaleria macrocarpa leaf (EEPML) on body weight and blood glucose levels of diabetic rat model. This was a quasi experimental study with post test only control group design. Fourty five male Sprague Dawley rats were classified into normal control group, diabetic control group with solvent, diabetic with 7mg/200g, 14mg/200g, and 28mg/200g of EEPML peroral administration, once a day for 3, 14 and 25 days. The diabetic rat model was made by streptozotocin and nicotinamide injection. Results : Statistical analysis of mean body weight and fasting blood glucose level showed there were significant differences between treatment groups. Conclusion : Administration of EEPML is able to affect the body weight and blood glucose level of diabetic rat model. Keywords: Diabetes Mellitus, Phaleria Macrocarpa, Ethanolic Extract, Streptozotocin, Antidiabetic


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2409 ◽  
Author(s):  
Tubagus Bahtiar Rusbana ◽  
Afifah Zahra Agista ◽  
Wahyu Dwi Saputra ◽  
Yusuke Ohsaki ◽  
Kouichi Watanabe ◽  
...  

Fermented rice bran (FRB), a prospective supplement, has been proven to ameliorate certain medical conditions. However, its nutraceutical effect on muscle atrophy has never been investigated. The present study aimed to evaluate the effect of FRB on muscle atrophy in a streptozotocin (STZ)-induced diabetic rat model. Three groups of Sprague-Dawley rats, namely the control, STZ, and FRB groups, were treated as follows. The diabetic groups (STZ and FRB) were injected intraperitoneally with STZ (40 mg/kg BW), whereas the control group was injected with the vehicle. The STZ and control groups were fed the AIN93M diet, and the FRB group was fed 10% of FRB based on the AIN93M diet. The diabetic groups had reduced muscle size compared to the control group; however, these changes were alleviated in the FRB group. Moreover, the FRB group had a significantly lower expression of FBXO32/Atrogin-1 and TRIM63/MuRF1 (p < 0.05) due to blocked NF-κB activation. In conclusion, the anti-inflammatory effect of FRB may be beneficial for ameliorating muscle atrophy in diabetic conditions.


Author(s):  
Guanghui Zheng ◽  
Fenglian He ◽  
Jing Xu ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
...  

Abstract Purpose To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). Methods Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. Results Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). Conclusion Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.


2015 ◽  
Vol 10 (10) ◽  
pp. 1934578X1501001
Author(s):  
Amitava Mandal ◽  
Vaskar Das ◽  
Pranab Ghosh ◽  
Shilpi Ghosh

We herein report the anti-diabetic effect of the natural friedelan tritepenoid, 4-oxa-3, 4-secofriedelan (cerin), isolated from cork tissue of Quercus suber L. and its oxygenated derivative, 4-oxa-3, 4-secofriedelan-3-oic acid (cerinox) in streptozotocin (STZ)-induced diabetic rat. Male Sprague Dawley rats were randomized into four groups: non-diabetic control (Group I), STZ-induced diabetic rats (Group II), STZ-induced diabetic rats treated with cerin (Group III), and STZ-induced diabetic rats treated with cerinox (Group IV). Administration of cerin (3mg/kg) and cerinox (3mg/kg) orally to STZ-diabetic rats for three weeks improved the body weight, reduced serum glucose level and activities of alkaline phosphatase, acid phosphatase, glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase, and restored liver antioxidant status.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lu Yin ◽  
Shen Zhao ◽  
JoongBum Moon ◽  
Peng Sun ◽  
Jiangang Wang ◽  
...  

Introduction: Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest. Hypothesis: We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Methods: A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC. Results: Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1). Conclusion: Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 844
Author(s):  
Khaidatul Akmar Kamaruzaman ◽  
Wan Mohd Aizat ◽  
Mahanem Mat Noor

Diabetes mellitus has a deleterious effect on the male reproductive system, especially on sperm quality and spermatogenesis. Gynura procumbens (G. procumbens) is a traditional herb known for its ability to improve the fertility of diabetes-induced male rats. This study was designed to identify the differential expression of sperm proteins after treatment with G. procumbens aqueous extract on diabetes-induced male rats. The sperm proteome was profiled using label-free shotgun proteomics analysis. Sprague Dawley rats used in this study were divided randomly into four groups. One group was a normal control group (healthy rats), while the three other groups were induced with 50 mg/kg  bodyweight (BW) of streptozotocin (STZ) to emulate the diabetic condition. The diabetic rats were divided into negative control (non-treated diabetic), metformin-treated (positive control) and G. procumbens aqueous extract-treated (450 mg/kg BW) groups. Oral treatments were administered for 14 consecutive days before the rats were euthanized. Total sperm protein samples were extracted from the caudal epididymis and run through SDS-PAGE. Later, samples were digested using trypsin before liquid chromatography-tandem mass spectrometry (Thermo Orbitrap Fusion) analysis. The acquired data were processed using MaxQuant and Perseus software. The mass spectrometry proteomics data is available through ProteomeXchange Consortium via the PRIDE partner repository, with the dataset identifier PXD011373.


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