scholarly journals Vasopeptidase Inhibitor Improves Coronary Dysfunction in Zucker Obese but not Zucker Diabetic Fatty (ZDF) Rats

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Christine L. Oltman ◽  
Travis L. Kleinschmidt ◽  
Lawrence J. Coppey ◽  
Eric P. Davidson ◽  
Mark A. Yorek
Keyword(s):  
Vasopeptidase Inhibitor ◽  
Zdf Rats

scholarly journals NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zheng-De Du ◽  
Wei Wei ◽  
Shukui Yu ◽  
Qing-Ling Song ◽  
Ke Liu ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Nadph Oxidase ◽  
Auditory Cortex ◽  
Auditory System ◽  
Auditory Brainstem ◽  
Secondary Symptom ◽  
Zucker Diabetic Fatty Rats ◽  
Brainstem Response ◽  
Zdf Rats ◽  
Nadph Oxidase 2

Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.

Disruption of Circadian Feeding Patterns in Obese ZDF Rats

2011 ◽  
Vol 165 (2) ◽  
pp. 334
Author(s):  
H.Y. Bhutta ◽  
D.B. Rhoads ◽  
S.W. Ashley ◽  
A. Tavakkolizadeh
Keyword(s):  
Feeding Patterns ◽  
Zdf Rats

scholarly journals Oxidative Stress-Dependent Impairment of Cardiac-Specific Transcription Factors in Experimental Diabetes

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5967-5974 ◽  
Author(s):  
Manuela Aragno ◽  
Raffaella Mastrocola ◽  
Claudio Medana ◽  
Maria Graziella Catalano ◽  
Ilenia Vercellinatto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Left Ventricle ◽  
Nuclear Factor Κb ◽  
Diabetic Rats ◽  
Nuclear Factor ◽  
Downstream Signaling ◽  
Zdf Rats ◽  
Myogenic Factors ◽  
Age Receptors

Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looked at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and prevents the oxidative damage induced by hyperglycemia in several experimental models. DHEA was given orally at a dose of 4 mg/rat per day for 21 d to rats with streptozotocin (STZ)-induced diabetes and genetic diabetic-fatty (ZDF) rats. Oxidative balance, advanced glycated end products (AGEs) and AGE receptors, cardiac myogenic factors, and myosin heavy-chain gene expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF rats. Oxidative stress induced by chronic hyperglycemia increased AGE and AGE receptors and led to activation of the pleoitropic transcription factor nuclear factor-κB. Nuclear factor-κB activation triggered a cascade of signaling, which finally led to the switch in the cardiac myosin heavy-chain (MHC) gene expression from the α-MHC isoform to the β-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE receptor activation in the heart of STZ-diabetic rats and ZDF rats and normalized downstream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2, and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy.

scholarly journals Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat

2016 ◽  
Vol 61 (1) ◽  
pp. 1501025 ◽  
Author(s):  
Felicia Goldsmith ◽  
Justin Guice ◽  
Ryan Page ◽  
David A. Welsh ◽  
Christopher M. Taylor ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Resistant Starch ◽  
No Reduction ◽  
Abdominal Fat ◽  
Zdf Rats

Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats

2008 ◽  
Vol 294 (1) ◽  
pp. E88-E96 ◽  
Author(s):  
Christoph M. Schummer ◽  
Ulrich Werner ◽  
Norbert Tennagels ◽  
Dieter Schmoll ◽  
Guido Haschke ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Oral Glucose ◽  
Glucose Load ◽  
Protein Levels ◽  
Zucker Diabetic Fatty Rats ◽  
Obese Rats ◽  
Zdf Rats ◽  
Dehydrogenase Complex

The mitochondrial pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes. We investigated carbohydrate oxidation (CHO) and the regulation of the PDC in lean and obese Zucker diabetic fatty (ZDF) rats during fed and starved conditions as well as during an oral glucose load without and with pharmacologically reduced levels of free fatty acids (FFA) to estimate the relative contribution of FFA on glucose tolerance, CHO, and PDC activity. The increase in total PDC activity (20–45%) was paralleled by increased protein levels (∼2-fold) of PDC subunits in liver and muscle of obese ZDF rats. Pyruvate dehydrogenase kinase-4 (PDK4) protein levels were higher in obese rats, and consequently PDC activity was reduced. Although PDK4 protein levels were rapidly downregulated (57–62%) in both lean and obese animals within 2 h after glucose challenge, CHO over 3 h as well as the peak of PDC activity (1 h after glucose load) in liver and muscle were significantly lower in obese rats compared with lean rats. Similar differences were obtained with pharmacologically suppressed FFA by nicotinic acid, but with significantly improved glucose tolerance in obese rats, as well as increased CHO and delta increases in PDC activity (0–60 min) both in muscle and liver. These results demonstrated the suppressive role of FFA acids on the measured parameters. Furthermore, the results clearly demonstrate a rapid reactivation of PDC in liver and muscle of lean and obese rats after a glucose load and show that PDC activity is significantly lower in obese ZDF rats.

Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart

2004 ◽  
Vol 286 (5) ◽  
pp. E725-E736 ◽  
Author(s):  
Peipei Wang ◽  
John C. Chatham
Keyword(s):  
Type 2 Diabetes ◽  
Recovery Of Function ◽  
Ischemic Injury ◽  
Left Ventricular ◽  
Low Flow ◽  
Rate Pressure Product ◽  
Control Group ◽  
Perfused Heart ◽  
Zdf Rats

The aim of this study was to determine whether the transition from insulin resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic changes in the myocardium that increase the sensitivity to ischemic injury. Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became progressively worse by 24 wk. In spontaneously beating hearts rate-pressure product (RPP) was depressed in the ZDF groups compared with age-matched Controls, primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF groups; however, this was accompanied by a significant decrease in left ventricular developed pressure. There was also greater contracture during LFI in the ZDF groups compared with the Control group; surprisingly, however, functional recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This improvement in recovery in the ZDF diabetic groups was independent of substrate availability, severity of ischemia, and duration of diabetes. These data demonstrate that, although the development of type 2 diabetes leads to progressive contractile and metabolic abnormalities during normoxia and LFI, it was not associated with increased susceptibility to ischemic injury.

scholarly journals Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

scholarly journals In Vitro and In Vivo Inhibition of the 2 Active Sites of ACE by Omapatrilat, a Vasopeptidase Inhibitor

Hypertension ◽  
2000 ◽  
Vol 35 (6) ◽  
pp. 1226-1231 ◽  
Author(s):  
Michel Azizi ◽  
Christine Massien ◽  
Annie Michaud ◽  
Pierre Corvol
Keyword(s):  
Active Sites ◽  
Vasopeptidase Inhibitor
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