Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry

1984 ◽  
Vol 62 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Chain Acyl ◽  
Uptake Activity ◽  
Streptozotocin Diabetic Rats ◽  
Developed Pressure

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

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.

Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV)

1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill
Keyword(s):  
Blood Glucose ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Plasma Lipid ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Vanadium Complex ◽  
Significant Correction ◽  
Streptozotocin Diabetic Rats

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.

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.

Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment

1983 ◽  
Vol 61 (5) ◽  
pp. 516-523 ◽  
Author(s):  
Arun G. Tahiliani ◽  
Rao V. S. V. Vadlamudi ◽  
John H. McNeill
Keyword(s):  
Insulin Treatment ◽  
Myocardial Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Myocardial Performance ◽  
Perfused Heart ◽  
Rat Hearts ◽  
Heart Preparation ◽  
Developed Pressure

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.

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.

Islet transplantation improves glucose oxidation and mechanical function in diabetic rat hearts

1993 ◽  
Vol 71 (12) ◽  
pp. 896-903 ◽  
Author(s):  
G. D. Lopaschuk ◽  
J. R. T. Lakey ◽  
R. Barr ◽  
R. Wambolt ◽  
A. B. R. Thomson ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Glucose Oxidation ◽  
Heart Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mechanical Function ◽  
Oxidation Rates ◽  
Rat Hearts ◽  
Low Glucose ◽  
Developed Pressure

In poorly controlled diabetes an impairment of glucose use can contribute to a depression in mechanical function of rat hearts. In this study we determined the effects of islet transplantation on glucose use and heart function in streptozotocin-induced diabetic rats. Myocardial function, glycolysis, and glucose oxidation were measured in isolated working hearts obtained from control, diabetic, and islet-transplanted diabetic Wistar–Furth rats. Islets (1200) were transplanted beneath the kidney capsule 2 weeks after a single i.v. dose of streptozotocin (55 mg/kg). The study consisted of three groups: (i) islet-transplanted diabetic rats, (ii) untreated diabetic controls, and (iii) normal controls. Following 11 weeks of monitoring, working hearts were perfused at a 11.5-mmHg (1 mmHg = 133.3 Pa) preload and 80-mmHg afterload, with buffer containing 11 mM [5-3H, 14C(U)]glucose, 1.2 mM palmitate, and 100 μU/mL insulin. In untreated diabetic rat hearts, glucose oxidation rates were markedly depressed compared with control hearts (30.4 ± 4 and 510 ± 68 nmol∙g−1 dry wt.∙min−1, respectively). Low glucose oxidation rates in diabetic rats were significantly improved in islet-transplanted animals (234 ± 39 nmol∙g−1 dry wt.∙min−1). The low glucose oxidation rates in untreated diabetic rat hearts were accompanied by an impaired mechanical function compared with control hearts, which was improved by islet transplantation (heart rate × developed pressure × 10−3 was 10.6 ± 0.9, 14.8 ± 1.3, and 14.8 ± 1.5 beats∙mmHg∙min−1, respectively). In the presence of insulin, steady-state rates of glycolysis were only slightly depressed in untreated diabetic rat hearts compared with control (1944 ± 436 and 2720 ± 265 nmol∙g−1 dry wt.∙min−1, respectively). However, during a reduction of coronary flow to 0.5 mL∙min−1, glycolytic rates accelerated in control and islet-transplanted rat hearts, but not in untreated diabetic rat hearts. These data show that the decrease in glucose use that occurs in untreated diabetic rats under both aerobic and ischemic conditions can be significantly alleviated by islet transplantation. The increase in glucose oxidation in aerobic hearts supports our previous studies, which suggest that increasing glucose oxidation can improve function in diabetic rat hearts.Key words: glucose oxidation, glycolysis, diabetes, islet transplantation.

Metformin improves cardiac function in isolated streptozotocin-diabetic rat hearts

1994 ◽  
Vol 266 (2) ◽  
pp. H714-H719 ◽  
Author(s):  
S. Verma ◽  
J. H. McNeill
Keyword(s):  
Isolated Heart ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Metformin Hydrochloride ◽  
Ventricular Contractility ◽  
Glucose Levels ◽  
Rat Hearts ◽  
Plasma Insulin Levels ◽  
Developed Pressure

The effects of metformin administration were studied in isolated perfused working hearts from control and diabetic rats. Control and streptozotocin-treated diabetic rats were treated for 8 wk with metformin hydrochloride. Treatment was initiated at 350 mg.kg-1 x day-1 and was gradually increased to a dose of 650 mg.kg-1 x day-1, which was maintained over a 6-wk period. Isolated heart performance was assessed under conditions of increasing preload to evaluate the performance of each heart to “stress.” Hearts from untreated diabetic rats exhibited a depressed response to increases in left atrial filling pressures from 17.5 to 22.5 cmH2O in terms of left ventricular developed pressure, ventricular contractility, and ventricular relaxation compared with age-matched untreated controls. The diabetic hearts also exhibited a delayed half time to relaxation at filling pressures from 15 to 22.5 cmH2O. The function curves were performed at a constant heart rate of 300 beats/min. These responses were restored to control values in diabetic rats treated with metformin. Metformin treatment did not affect the ventricular responses in control rats. Metformin reduced plasma glucose levels in the diabetic rats from 24.3 to 14.4 mM without any increase in the plasma insulin levels. The diabetic group had higher triglycerides than age-matched untreated control rats, and metformin administration in diabetic rats reduced triglyceride levels to control values but had no effect in control rats. In conclusion, metformin administration improves cardiac performance in streptozotocin-diabetic rats under conditions of increasing preload.

The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines

1983 ◽  
Vol 61 (5) ◽  
pp. 439-448 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Sidney Katz ◽  
John H. McNeill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Heart Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Microsomal Preparation ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Gradual Onset ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
Long Chain

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2–5.0 μM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62–73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations < 7 μM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.

Ischemic preconditioning prevents I/R-induced alterations in SR calcium-calmodulin protein kinase II

2000 ◽  
Vol 278 (6) ◽  
pp. H1791-H1798 ◽  
Author(s):  
Mitsuru Osada ◽  
Thomas Netticadan ◽  
Kenichi Kawabata ◽  
Kohji Tamura ◽  
Naranjan S. Dhalla
Keyword(s):  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
Contractile Activity ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Beneficial Effects ◽  
Protein Kinase Ii ◽  
Uptake Activity

Although Ca2+/calmodulin-dependent protein kinase II (CaMK II) is known to modulate the function of cardiac sarcoplasmic reticulum (SR) under physiological conditions, the status of SR CaMK II in ischemic preconditioning (IP) of the heart is not known. IP was induced by subjecting the isolated perfused rat hearts to three cycles of brief ischemia-reperfusion (I/R; 5 min ischemia and 5 min reperfusion), whereas the control hearts were perfused for 30 min with oxygenated medium. Sustained I/R in control and IP groups was induced by 30 min of global ischemia followed by 30 min of reperfusion. The left ventricular developed pressure, rate of the left ventricular pressure, as well as SR Ca2+-uptake activity and SR Ca2+-pump ATPase activity were depressed in the control I/R hearts; these changes were prevented upon subjecting the hearts to IP. The beneficial effects of IP on the I/R-induced changes in contractile activity and SR Ca2+ pump were lost upon treating the hearts with KN-93, a specific CaMK II inhibitor. IP also prevented the I/R-induced depression in Ca2+/calmodulin-dependent SR Ca2+-uptake activity and the I/R-induced decrease in the SR CaMK II activity; these effects of IP were blocked by KN-93. The results indicate that IP may prevent the I/R-induced alterations in SR Ca2+ handling abilities by preserving the SR CaMK II activity, and it is suggested that CaMK II may play a role in mediating the beneficial effects of IP on heart function.

scholarly journals Oxidative Stress in Rats After 60 Days of Hypergalactosemia or Hyperglycemia

2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glutathione Disulfide ◽  
Hepatic Lipid Peroxidation ◽  
Streptozotocin Diabetic Rats

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.

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