Cardiac function in spontaneously diabetic BB rats treated with low and high dose insulin

1989 ◽  
Vol 67 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Brian Rodrigues ◽  
Gail M. McGrath ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Calcium Transport ◽  
Heart Function ◽  
Insulin Dose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Bb Rat ◽  
High Dose ◽  
Drug Induced ◽  
Bb Rats

Cardiac abnormalities observed in animals with drug-induced diabetes may be due to the direct cardiotoxic effect of the drugs or factors not related to the diabetic state. The purpose of this investigation was to examine cardiac sarcoplasmic reticular (SR) calcium transport and heart function in the BB rat, a strain in which diabetes occurs spontaneously and clearly resembles insulin-dependent diabetes in humans. Complete insulin withdrawal for 2 or 4 days from BB diabetic rats leads to a spectrum of metabolic derangements including a loss of body weight, hyperglycemia, and elevated triglyceride levels confirming the insulin dependence of this model. The present study involved treating BB diabetic rats with a low (hyperglycemic) and high (normoglycemic) insulin dose for 12 weeks after the detection of glycosuria. The hearts from these animals were then isolated, and SR Ca2+ transport and heart function (using isolated perfused working hearts) were examined and compared with BB nondiabetic littermates or Wistar controls. Strain-related differences were found in ATP-dependent SR Ca2+ transport between the Wistar and BB rats. There were, however, no significant diabetes-related differences in SR Ca2+ transport between the low dose insulin treated diabetic group (LD) and the high dose insulin treated diabetic group (HD) or the nondiabetic littermates. Plasma lipid concentrations of the LD and HD BB rats and nondiabetic littermates were also generally higher than those of control Wistar rats indicating strain-related but not diabetes-related differences. In addition, there were no differences in cardiac function between the LD and BB nondiabetic littermates or Wistar controls. These studies suggest that since persistent hyperglycemia in the LD BB rat produced no significant physiological abnormalities in the heart, other factors must be contributing to the depression of heart function noted during diabetes.Key words: diabetes, BB rat, sarcoplasmic reticular calcium transport, heart function.

Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats

1990 ◽  
Vol 68 (4) ◽  
pp. 514-518 ◽  
Author(s):  
Brian Rodrigues ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Insulin Dose ◽  
Cardiac Contractility ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Myosin Atpase ◽  
Bb Rat ◽  
Relaxation Rates ◽  
Bb Rats

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.Key words: diabetes, cardiac function, Wistar BB rat, myosin ATPase, cardiomyopathy.

Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency

2000 ◽  
Vol 349 (1) ◽  
pp. 353-356 ◽  
Author(s):  
Cynthia J. MEININGER ◽  
Rebecca S. MARINOS ◽  
Kazuyuki HATAKEYAMA ◽  
Raul MARTINEZ-ZAGUILAN ◽  
Jose D. ROJAS ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Diabetic Rats ◽  
Bb Rat ◽  
No Production ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
Bb Rats ◽  
Metabolic Basis ◽  
Rate Limiting

Endothelial cells (EC) from diabetic BioBreeding (BB) rats have an impaired ability to produce NO. This deficiency is not due to a defect in the constitutive isoform of NO synthase in EC (ecNOS) or alterations in intracellular calcium, calmodulin, NADPH or arginine levels. Instead, ecNOS cannot produce sufficient NO because of a deficiency in tetrahydrobiopterin (BH4), a cofactor necessary for enzyme activity. EC from diabetic rats exhibited only 12% of the BH4 levels found in EC from normal animals or diabetes-prone animals which did not develop disease. As a result, NO synthesis by EC of diabetic rats was only 18% of that for normal animals. Increasing BH4 levels with sepiapterin increased NO production, suggesting that BH4 deficiency is a metabolic basis for impaired endothelial NO synthesis in diabetic BB rats. This deficiency is due to decreased activity of GTP-cyclohydrolase I, the first and rate-limiting enzyme in the de novo biosynthesis of BH4. GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells.

Cardiac function in spontaneously hypertensive diabetic rats

1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Working Heart ◽  
Diabetes Induction

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.

Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats

1999 ◽  
Vol 86 (3) ◽  
pp. 812-818 ◽  
Author(s):  
Kiminori Kato ◽  
Donald C. Chapman ◽  
Heinz Rupp ◽  
Anton Lukas ◽  
Naranjan S. Dhalla
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Binding Sites ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Carnitine Palmitoyltransferase ◽  
Heart Weight ◽  
High Affinity

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3′,-5-triiodo-l-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.

scholarly journals Effect of Vitex Agnus-Castus Ethanolic Extract on Sex Hormones in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Author(s):  
Fatemeh Soleymanzadeh ◽  
Minoo Mahmoodi ◽  
Siamak Shahidi
Keyword(s):  
Sex Hormones ◽  
Experimental Studies ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Female Rats ◽  
Control Group ◽  
Diabetic Patients ◽  
High Dose ◽  
Fruit Extract ◽  
Agnus Castus

Objective: Diabetes mellitus is recognized as one of the serious global health problems. There are evidences regarding the high prevalence of sexual dysfunction in diabetic patients. Experimental studies revealed a positive effect of Vitex agnus-castus (Vitex), on sexual function and behaviors. In this research, the effect of Vitex on sexual hormones in streptozotocin-(STZ) induced diabetic rats was investigated. Materials and methods: A Thirty adult female Wistar rats were divided into five groups. 1-control group (non-diabetic), 2- diabetic group (received normal saline) and three induced diabetic groups treated with different doses (400, 200 and 100 mg/kg) of Vitex. Treatment groups received Vitex fruit extract by gavage for 7 days. The levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estrogen in serum were measured. Results: Levels of LH, FSH, estrogen and progesterone and average body weight was lower in diabetic group compared to control group (p <0.010). Animals received high dose of Vitex fruit extract (400mg/kg) had significantly higher levels of serum LH, FSH, estrogen and progesterone compared to diabetic group (p < 0.010). In animals receiving minimum dose (100mg/kg) of Vitex, no difference was observed compared to diabetic group (p > 0.010). Conclusion: It can be concluded that Vitex fruit extract probably has regulatory effect on diabetes-induced change in the levels of sex hormones in female rats. Vitex fruit extract can improve serum levels of sex hormones in an animal model of STZ-induced diabetes.

scholarly journals Nobiletin Protects Against Diabetes-induced Testicular Injury via Hypophysis-gonadal Axis Up-regulation and Amelioration of Oxidative Stress

2021 ◽  
Author(s):  
Marwa Salah ◽  
Khadiga Ahmed Ismail ◽  
sally mostafa khadrawy
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Androgen Receptors ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
High Dose ◽  
Testicular Injury ◽  
Pro Inflammatory Cytokines

Abstract Background: Testicular injury is one of the most serious problems of Diabetes mellitus. The present study aims to compare the effect of two different doses of nobiletin and the probable mechanisms against diabetes-induced testicular impairment in rats. Methods and Results: Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin (10 mg/kg) or (25 mg/kg) daily and orally for 30 days. Diabetic rats displayed a significant elevation in glucose, glycosylated hemoglobin (HbA1c), homeostasis model of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. Levels of serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes with positive caspase-3 and decreased Androgen receptors (AR) immunoexpressions were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. Gene and protein manifestation of LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) was markedly down-regulated in testicular tissues of diabetic group, an effect which was markedly increased with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation, and caspase-3 immuno-expression and improved the activity of the antioxidant enzymes and AR in testicular tissues of diabetic group. Conclusion: Both doses showed protective effects against diabetes-induced testicular injury by diminution of oxidative stress, hyperglycemia, inflammation, caspase-3 and up-regulation of the hypophysis-gonadal axis and androgen receptors. The high dose of nobiletin was more effective than the lower dose.

Hypertriglyceridemia in experimental diabetes: relationship to cardiac dysfunction

1994 ◽  
Vol 72 (5) ◽  
pp. 447-455 ◽  
Author(s):  
Brian Rodrigues ◽  
Paul F. Grassby ◽  
Mary L. Battell ◽  
Stephanie Y. N. Lee ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Plasma Triglyceride ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Of Increase

The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test die hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (±dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with die exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent die onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in die diabetic rat at this time point.Key words: diabetes, triglycerides, heart function, glucose oxidation.

scholarly journals Traditional Chinese Medicine Formulation Huangqi Jianzhong Tang Improves Cardiac Function after Myocardial Infarction in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ya-Ru Bao ◽  
Wen-Yi Jiang ◽  
Jia-Yu Yu ◽  
Jing-Wei Chen ◽  
Guo-Xing Zhang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Heart Function ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
High Dose ◽  
Therapeutic Effects ◽  
Myocardial Infarct Size ◽  
Radix Paeoniae Alba

Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. The present study aims to evaluate the possible effects of HQJZT on cardiac function in acute myocardial infarction (AMI) and related mechanism. AMI model was established by ligation of the left anterior descending coronary artery followed by one-week HQJZT treatment. Survival rate was calculated. Rat heart function was assessed by heart performance analysis system. 5-Triphenyltetrazolium chloride (TTC) staining was used to observe myocardial infarct size. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and western blot were applied to evaluate tissue apoptotic level. Treatment with high dose of HQJZT improved cardiac function, reduced infarct size, number of apoptotic cells and expression of apoptotic proteins, Bax (a proapoptotic protein), and increased expression of antiapoptotic protein, Bcl2. However, enalapril (an angiotensin-converting enzyme inhibitor) treatment did not show marked improvement of these parameters. Our present data suggest that HQJZT has potential therapeutic effects to improve cardiac function by regulation of apoptotic signaling pathway.

scholarly journals Elucidation of The Effects and Underlying Mechanism of Aerobic Interval Training Combined With Liraglutide On Diabetic Cardiomyopathy

2022 ◽  
Author(s):  
Huan Cai ◽  
Linling Zhou ◽  
Jingqin Liu ◽  
Zelin Li ◽  
Shuchun Chen
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Cell Function ◽  
Heart Function ◽  
Intervention Group ◽  
Interval Training ◽  
Myocardial Tissue ◽  
High Dose ◽  
Relative Expression ◽  
Aerobic Interval Training

Abstract objective: This study intended to explore the hypoglycemic and cardioprotective effects of 8-week aerobic interval training combined with liraglutide and elucidate the underlying mechanisms.Method: Male Wistar rats were randomly divided into 5 groups - normal control (CON), diabetic cardiomyopathy (DCM), high-dose liraglutide (DH), low-dose liraglutide DL , and aerobic interval training combined with liraglutide (DLE). The cardiac function of rats ,the FBG the levels of fasting insulin (FIN), HbA1c, the total collagen content , AGEs, the mRNA expression of myocardial remodeling genes BNP, GSK3β, α-MHC, and β-MHC ,the expression of GLP-1 and GLP-1R proteins, Insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) was analyze. Results: During the intervention, the FBG in each intervention group significantly decreased compared to the DCM group. After 8 weeks,the DH, DL, and DLE groups showed improved blood glucose-related indices and cleared the accumulated AGEs in the DCM groups. The heart function in the DLE groups was significantly improved than that in the DH and DL groups. The relative expression of BNP mRNA in the DH, DL, and DLE groups significantly reduced compared to the CON and the DCM group .Compared to the DCM group,the relative expression of α-MHC mRNA increased significantly and β-MHC mRNA decreased notably in the myocardium of the DH, DL, and the DLE group.The expression of GLP-1 in the myocardial tissue of rats in the DH group was higher than that in the DL and DLE groups. GLP-1R expression in the myocardial tissue in the DLE group was higher than that in the DH , DL and the DCM groups .Conclusion: Liraglutide combined with AIT intervention significantly reduced FBG and the fluctuations in FBG, alleviated myocardial fibrosis, improved cardiac function in DCM rats, supporting the efficacy of the combined pharmaceutical and physical intervention, and reduced the cost of treatment.

Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats

1983 ◽  
Vol 245 (6) ◽  
pp. H969-H976 ◽  
Author(s):  
G. D. Lopaschuk ◽  
A. G. Tahiliani ◽  
R. V. Vadlamudi ◽  
S. Katz ◽  
J. H. McNeill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Transport ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Heart Apparatus

Cardiac sarcoplasmic reticulum (SR) function and SR levels of long-chain (LC) acylcarnitines were determined in streptozotocin-induced diabetic rats treated with insulin or D,L-carnitine. ATP-dependent calcium transport was significantly depressed in cardiac SR isolated from untreated diabetic rats compared with control rats. Diabetic rat cardiac SR levels of LC acylcarnitines were also significantly elevated. Various parameters of heart function (left ventricular developed pressure, +dP/dT, and -dP/dT), as determined on an isolated working heart apparatus, were found to be depressed in untreated diabetic rats. Cardiac SR isolated from diabetic rats treated throughout the study period with insulin or D,L-carnitine did not have elevated levels of LC acylcarnitines associated with SR membrane nor was SR calcium transport activity depressed. Heart function in the diabetic rats treated with insulin was similar to control rat hearts but heart function remained depressed in diabetic rats treated with D,L-carnitine. The data suggest that the LC acylcarnitines are involved in the observed impairment of cardiac SR function in diabetic rats. Other factors, however, must be contributing to the depression in heart function noted in these animals.

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