Mechanisms Underlying Contractile Dysfunction in Streptozotocin-Induced Type 1 and Type 2 Diabetic Cardiomyopathy

Bracken, Nicolas; Singh, Jaipaul; Winlow, William; Howarth, Frank Christopher

doi:10.1007/978-1-4419-9232-1_30

Cited by 9 publications

(20 citation statements)

References 89 publications

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“…The results also show that the whole heart as well as the atria, and right and left ventricles have significantly reduced weights in the diabetic rats compared to the control animals. These results are in total agreement in previous studies employing the STZ‐induced diabetic rats 5,6,14,16 . The reduction in body weight as well as the weight of the heart in diabetic animals may be due either to the diabetes itself or the animals eating less 19 …”

Section: Discussionsupporting

confidence: 92%

“…This model displays similar features of the human form of DM 7 . Previous studies have shown that a derangement in cellular and subcellular Ca 2+ homeostasis may be associated with impairment of the diabetic heart 5,6 . There is much evidence that L‐type Ca 2+ channel, SERCA pump, and the Na + /Ca 2+ exchanger are all deranged as DM develops 9–12 .…”

Section: Introductionsupporting

confidence: 52%

“…An incision was made in the abdomen and the heart rapidly excised and placed in ice‐cold buffer solution (mM): 130 NaCl; 5.2 CaCl 2 , 1.0 MgCl 2 , 0.4 NaH 2 PO 4 , 5 hepes, 10 glucose, 10 taurine, 10 creatine, and pH 7.3. In some experiments, ventricular myocytes were isolated with the buffer solution containing collagenase (0.75 mg mL −1 ; Sigma (Dorset, UK)) as previously described 5,8,13,14,16 . Cells were used during a period of 1–8 h after isolation to measure either contraction (shortening) using a video edge system or intracellular free Ca 2+ free concentration [Ca 2+ ] i after loading with Fura 2 (AM) using established methods 5,8,13,14,16 …”

Section: Methodsmentioning

confidence: 99%

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Effect of Streptozotocin‐Induced Type 1 Diabetes Mellitus on Contraction, Calcium Transient, and Cation Contents in the Isolated Rat Heart

Singh

Chonkar

Bracken

et al. 2006

Annals of the New York Academy of Sciences

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Cations play major physiological and biochemical roles in the excitation-contraction coupling processes in the heart. This study investigated the effect of streptozotocin (STZ)-induced type I diabetes mellitus (DM) on contraction, calcium transient [Ca2+]i, and cation contents in the isolated rat heart compared to age-matched control. Diabetes rats weighed significantly (P < 0.05) less compared to control. They also had significantly (P < 0.05) elevated blood glucose compared to control. The whole heart, as well as the atria, right and left ventricles of the diabetic heart weighed significantly (P < 0.05) less compared to hearts from age control rats. The force of contraction and time to peak (t-pk) contraction in diabetic ventricular myocytes increased significantly (P < 0.05) compared to control. By contrast, these parameters did not change for the Ca2+ transient except for the time to half (t(1/2)) relaxation. The levels of sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), iron (Fe2+), copper (Cu2+), and zinc (Zn2+) in the hearts varied from diabetic compared to control animals. The results indicate that 6-8 weeks of STZ-induced DM is associated with marked changes in contraction and in cation contents of the heart. The delay in the t(1/2) relaxation of the Ca2+ transient may be responsible for the elevated contraction seen in the diabetic heart. Moreover, the changes in cation contents in the heart may be responsible for abnormal cardiac rhythms and activity during DM.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionsupporting

confidence: 52%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Streptozotocin‐Induced Type 1 Diabetes Mellitus on Contraction, Calcium Transient, and Cation Contents in the Isolated Rat Heart

Singh

Chonkar

Bracken

et al. 2006

Annals of the New York Academy of Sciences

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“…One major long‐term complication of diabetes is cardiomyopathy, in which the heart is unable to pump blood efficiently. This could be due to several factors including reduced contraction or derangement in cellular Ca 2+ homeostasis or both 17,18,23 . In previous studies, we have shown that STZ‐induced DM is not associated with reduced amplitude of contraction in electrically stimulated ventricular cardiomyocytes 34 at 1 Hz compared to age‐matched control.…”

Section: Discussionmentioning

confidence: 72%

“…DM was induced in male Wistar rats (200–250 g body weight) by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) (60 mg kg −1 body weight) dissolved in a citrate acid buffer solution 23 . Age‐matched control rats received an equivalent volume of citrate acid buffer solution alone.…”

Section: Methodsmentioning

confidence: 99%

Effects of Streptozotocin‐Induced Diabetes on Contraction and Calcium Transport in Rat Ventricular Cardiomyocytes

Bracken¹,

Howarth²,

Singh³

2006

Annals of the New York Academy of Sciences

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Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)-induced type 1 DM on contraction, L-type calcium (Ca2+) current (I(Ca(2+)L)), and on cytosolic calcium concentrations [Ca2+]i in ventricular myocytes of the rat heart. After 4-10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age-matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of I(Ca(2+)L) and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range -10 mV to +20 mV and -30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age-matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine-evoked time to half relaxation of the Ca2+ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl2). It is concluded that the diabetes-induced voltage-dependent decrease in contraction is associated with reduced Ca2+ channel activities and prolonged diastolic cytosolic Ca2+ compared to age-matched control. Taken together, the results suggest that Ca2+ homeostasis is deranged during DM and this may be expressed at the level of the Na+/Ca2+ exchanger.

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Structural changes in the myocardium during diabetes-induced cardiomyopathy

Adeghate

Singh

2013

Heart Fail Rev

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Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 250 million people globally. It costs the worldwide health services almost £800 billion annually to diagnose, treat and care for patients with diabetes. DM is predicted to rise to 350 million by 2030. If left unmanaged, DM can lead to numerous long-term complications including micro- and macro-angiopathy and heart failure (HF). Most diabetics usually die as a result of HF resulting from diabetes-induced coronary artery disease and cardiomyopathy. Coronary artery disease and cardiomyopathy are normally preceded by hyperglycaemia (HG). This review examines the structural changes, which occur within the myocardium and cardiomyocytes during exposure of the heart to diabetes-induced HG and HG-induced oxidative stress. HG and the resulting oxidative stress are associated with marked myocardial hypertrophy and fibrosis compared to control heart. At the ultrastructural level, cardiomyocytes subjected to chronic HG and subsequent oxidative stress display swollen mitochondria, reduced mitochondrial number and defective myofibrils and intercalated discs. Evidence from many studies shows that both type 1 and type 2 diabetes-induced HG can cause myocardial fibrosis, mitochondriopathy, myocyte hypertrophy and deranged myofibrils. All of these structural changes may eventually result in HF if left untreated.

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Mechanisms Underlying Contractile Dysfunction in Streptozotocin-Induced Type 1 and Type 2 Diabetic Cardiomyopathy

Cited by 9 publications

References 89 publications

Effect of Streptozotocin‐Induced Type 1 Diabetes Mellitus on Contraction, Calcium Transient, and Cation Contents in the Isolated Rat Heart

Effect of Streptozotocin‐Induced Type 1 Diabetes Mellitus on Contraction, Calcium Transient, and Cation Contents in the Isolated Rat Heart

Effects of Streptozotocin‐Induced Diabetes on Contraction and Calcium Transport in Rat Ventricular Cardiomyocytes

Structural changes in the myocardium during diabetes-induced cardiomyopathy

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