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The chronic effects of neonatal alloxan-induced diabetes mellitus on ventricular myocyte shortening and cytosolic Ca2+

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Abstract

Diabetes mellitus is a serious global health problem, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The chronic effects of neonatal alloxan- (ALX) induced diabetes mellitus on ventricular myocyte contraction and intracellular Ca2+ transport have been investigated. Ventricular myocyte shortening was measured with a video edge detection system and intracellular Ca2+ was measured in fura-2 loaded cells by fluorescence photometry. Diabetes was induced in 5-day old male Wistar rats by a single intraperitoneal injection of ALX (200 mg/kg body weight). Experiments were performed 12 months after ALX treatment. Fasting blood glucose was elevated and blood glucose at 60, 120 and 180 min after a glucose challenge (2 g/kg body weight, intraperitoneal) was elevated in diabetic rats compared to age-matched controls. Amplitude of shortening was significantly (P < 0.05) reduced in electrically stimulated myocytes from diabetic hearts (5.70 ± 0.24%) compared to controls (6.48 ± 0.28%). Amplitude of electrically evoked Ca2+ transients was also significantly (P < 0.05) reduced in myocytes from diabetic hearts (0.11 ± 0.01 fura-2 ratio units) compared to controls (0.15 ± 0.01 fura-2 ratio units). Fractional sarcoplasmic reticulum Ca2+ release was not significantly (P > 0.05) altered in myocytes from diabetic heart (0.70 ± 0.03 fura-2 ratio units) compared to controls (0.72 ± 0.03 fura-2 ratio units). Amplitude of caffeine-stimulated Ca2+ transients was significantly (P < 0.05) reduced in myocytes from diabetic hearts (0.43 ± 0.02 fura-2 ratio units) compared to controls (0.51 ± 0.03 fura-2 ratio units). Area under the caffeine-evoked Ca2+ transient was significantly (P < 0.05) reduced in myocytes from diabetic heart (0.77 ± 0.06 Vsec) compared to controls (1.14 ± 0.12 Vsec). Intracellular Ca2+ refilling rate during electrical stimulation following application of caffeine was significantly (P < 0.05) slower in myocytes from diabetic heart (0.013 ± 0.001 V/sec) compared to controls (0.031 ± 0.007 V/sec). Depressed shortening may be partly attributed to depressed sarcoplasmic reticulum Ca2+ transport in myocytes from neonatal ALX-induced diabetic rat heart.

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Acknowledgments

Grant from UAE University.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE

    Frank Christopher Howarth, Zahra Hassan & Muhammad Anwar Qureshi

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  1. Frank Christopher Howarth
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  2. Zahra Hassan
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  3. Muhammad Anwar Qureshi
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Correspondence to Frank Christopher Howarth.

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Howarth, F.C., Hassan, Z. & Qureshi, M.A. The chronic effects of neonatal alloxan-induced diabetes mellitus on ventricular myocyte shortening and cytosolic Ca2+ . Mol Cell Biochem 347, 71–77 (2011). https://doi.org/10.1007/s11010-010-0613-4

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  • DOI: https://doi.org/10.1007/s11010-010-0613-4

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