Depressed cardiac sarcoplasmic reticular function from diabetic rats

Penpargkul, Somsong

doi:10.1016/0022-2828(81)90318-7

Cited by 247 publications

(104 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These changes have been attributed to a reduced ability to sequester calcium into the SR (8,22), which primarily determines the speed of cardiac relaxation and has several consequences on other parameters of cardiac contraction (23). A diminished calcium uptake into the SR leads to a reduction of calcium stored within this organelle.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies suggest a dysfunctional sarcoplasmic reticulum (SR), leading to altered intracellular calcium handling in cardiac myocytes, might be involved in the development of this disease. A reduced sequestration of calcium into the SR could readily explain the prolonged cardiac relaxation observed in diabetic cardiomyopathy (8). As a consequence, the SR calcium content declines, leading to a reduced systolic calcium release and therefore a weaker cardiac contraction (9,10).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Improves Myocardial Contractility in Diabetic Cardiomyopathy

et al. 2002

View full text Add to dashboard Cite

Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to direct changes in heart muscle function independent of vascular disease. An important contributor to contractile dysfunction in the diabetic state is an impaired sarcoplasmic reticulum (SR) function, leading to disturbed intracellular calcium handling. We investigated whether overexpression of the SR calcium pump (SERCA2a) in transgenic mice could reduce the impact of diabetes on the development of cardiomyopathy. Diabetes was induced by streptozotocin injection (200 mg/kg), and left ventricular (LV) function was analyzed in isolated hearts 3 weeks later. In diabetic hearts systolic LV pressure was decreased by 15% and maximum speed of relaxation (؊dP/dt) by 34%. Functional changes were also assessed in isolated papillary muscles. Active force was reduced by 61% and maximum speed of relaxation by 65% in the diabetic state. The contractile impairment was accompanied by a 30% decrease in SERCA2a protein in diabetic mice. We investigated whether increased SERCA2a expression in transgenic SERCA2a-overexpressing mice could compensate for the diabetes-induced decrease in cardiac function. Under normal conditions, SERCA2a overexpressors show improved contractile performance relative to wild-type (WT) mice (؊dP/dt: 3,169 vs. 2,559 mmHg/s, respectively). Measurement of LV function in hearts from diabetic SERCA2a mice revealed systolic and diastolic functions that were similar to WT control mice and markedly improved relative to diabetic WT mice (؊dP/dt: 2,534 vs. 1,690 mmHg/s in diabetic SERCA2a vs. diabetic WT mice, respectively). Similarly, the contractile behavior of isolated papillary muscles from diabetic SERCA2a mice was not different from that of control mice. SERCA2a protein expression was higher (60%) in diabetic SERCA2a mice than WT diabetic mice. These results indicate that overexpression of SERCA2a can protect diabetic hearts from severe contractile dysfunction, presumably by improving the calcium sequestration of the SR.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Improves Myocardial Contractility in Diabetic Cardiomyopathy

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Membrane fractions enriched with SR were isolated either from single left ventricles or from pools of two left ventricles, as determined by preliminary studies of SR protein yield, by the method of Penpargkul et al 9 with minor modifications. The need for pooling explains the differences in total sample size between groups in, for example, Tables 1 and 5.…”

Section: Sarcoplasmic Reticulum Calcium Uptakementioning

confidence: 99%

Ventricular relaxation of diabetic spontaneously hypertensive rat.

1990

View full text Add to dashboard Cite

Diabetes, and possibly the hypothyroidism that attends diabetes, impairs mechanical relaxation of ventricular muscle, in part by depressing the rate of Ca 2+ uptake by sarcoplasmic reticulum. Left ventricular hypertrophy exacerbates the adverse effects of diabetes on cardiac performance, but its effects on relaxation variables have not been well characterized. We examined the impact of streptozotocin-induced diabetes (8 weeks) on ventricular pressure load-dependent relaxation and sarcoplasmic reticular calcium uptake of hearts from spontaneously hypertensive rats and Wistar-Kyoto rats. Subsets of diabetic hypertensive rats were treated with either insulin (10 units/kg/day) or triiodothyronine (8-10 /tg/kg/day). Diabetes impaired load-dependent relaxation and depressed sarcoplasmic reticular calcium uptake only in spontaneously hypertensive rat hearts. Either insulin or triiodothyronine treatment prevented the diabetes-induced depressions of both mechanical and biochemical indexes of relaxation. The results suggest that 1) hypertrophic ventricles of spontaneously hypertensive rats are more susceptible to the detrimental effects of diabetes on relaxation indexes than are the nonhypertrophic Wistar-Kyoto rat ventricles, and 2) the hypothyroidism that attends diabetes may contribute to the impaired relaxation of diabetic spontaneously hypertensive rat left ventricle. have an impact on ventricular relaxation. The presence of LVH alone may or may not be associated with impaired relaxation. "17 However, when diabetes coexists with LVH in the spontaneously hypertensive rat (SHR), the rate of left ventricular pressure decline of perfused hearts is more profoundly depressed when compared with the effects of diabetes in normotensive rat strains. -13 Isometric relaxation is also prolonged in hypertrophic papillary muscles from the diabetic renovascular hypertensive rat.12 These results would suggest that combined effects of diabetes and LVH on SR Ca 2+ uptake might be more pronounced than the influence of either condition individually. However, the interaction between diabetes and LVH on the relation between myocardial relaxation and SR calcium uptake has not been characterized.Reduced serum levels of thyroid hormones are often associated with diabetes, l *-n and this hypothyroidism (or "low thyroid state") may contribute to diabetic cardiomyopathy. Thyroid hormone deficiencies, like diabetes, can lead to prolonged relaxation and depressed rates of SR calcium uptake in the myocardium. 18- 19 The effects of hypothyroidism on these measurements are well correlated, both in nonhypertrophic and hypertrophic ventricles. 20 Treatment of the diabetic SHR with triiodothyronine (T 3 ) effectively prevents the resultant cardiac dysfunction, 21 -22 but the influence of T 3 treatment in nonhypertensive diabetic rat models is inconsistent.

show abstract

“…[1][2][3][4] The subcellular mechanisms responsible for cardiomyopathy are unknown. However, several cellular defects, including depressions in sarcoplasmic reticular Ca 2ϩ uptake, 5 Na ϩ -K ϩ pump, 6 sarcolemmal Ca 2ϩ pump, Na ϩ -Ca 2ϩ exchanger activities, 7 and the alteration of mitochondrial functions, 8 have been suggested to be contributors to the development of this disease. The net result of these changes in Ca 2ϩ homeostasis causes an intracellular Ca 2ϩ overload, thereby resulting in cellular damage and, ultimately, diabetic cardiomyopathy.…”

mentioning

confidence: 99%

Troglitazone Inhibits Voltage-Dependent Calcium Currents in Guinea Pig Cardiac Myocytes

et al. 1999

View full text Add to dashboard Cite

Background-It has been suggested that intracellular Ca 2ϩ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy. Troglitazone, an insulin-sensitizing agent, is a promising therapeutic agent for diabetes and has been shown to prevent diabetes-induced myocardial changes. To elucidate the underlying mechanism of troglitazone action on cardiac myocytes, the effects of troglitazone on voltage-dependent Ca 2ϩ currents were examined and compared with classic Ca 2ϩ antagonists (verapamil and nifedipine).

show abstract

Depressed cardiac sarcoplasmic reticular function from diabetic rats

Cited by 247 publications

References 15 publications

Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Improves Myocardial Contractility in Diabetic Cardiomyopathy

Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Improves Myocardial Contractility in Diabetic Cardiomyopathy

Ventricular relaxation of diabetic spontaneously hypertensive rat.

Troglitazone Inhibits Voltage-Dependent Calcium Currents in Guinea Pig Cardiac Myocytes

Contact Info

Product

Resources

About