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Stable microtubules contribute to cardiac dysfunction in the streptozotocin-induced model of type 1 diabetes in the rat

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Abstract

Cardiac microtubule stability is increased in the streptozotocin (STZ) model of type 1 diabetes. Here, we investigate the reason for increased microtubule stability, and the functional consequences of stable microtubule disruption. Ventricular myocytes were isolated from rats at 8–12 weeks after injection of STZ. A 10% increase in microtubule density, but no difference in the ratio of microtubule-associated protein 4 (MAP4) to tubulin was seen in myocytes from STZ rats. Functionally, STZ myocytes showed a tendency for reduced shortening and intracellular Ca2+ ([Ca2+] i ) transient amplitude, and a significant prolongation of time to peak (ttp) shortening and [Ca2+] i . Although microtubules in STZ myocytes were less sensitive to the microtubule disruptor nocodazole (NOC; 33 μM) than control myocytes, we only saw marked functional consequences of microtubule disruption by NOC in myocytes from diabetic animals. NOC increased shortening and [Ca2+] i transient amplitude in STZ myocytes by 45 and 24%, respectively (compared with 4 and 6% in controls). Likewise, NOC decreased ttp shortening and [Ca2+] i only in STZ myocytes, such that these parameters were no longer different between the two groups. In conclusion, stable microtubules in diabetes are not associated with an increase in MAP4, but are functionally relevant to cardiac dysfunction in diabetes, regulating both [Ca2+] i and shortening.

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Acknowledgment

This work was funded by the British Heart Foundation and by a travel bursary from the British Council (Abu Dhabi, U.A.E).

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Authors and Affiliations

  1. Research Institute of Membrane and Systems Biology, University of Leeds, Worsley Building, Leeds , LS2 9JT, UK

    Anthony O’Connell, Ed White & Sarah Calaghan

  2. Faculty of Life Sciences, Core Technology Facility, University of Manchester, 46 Grafton St, Manchester , M13 9PT, UK

    Holly Shiels

  3. Department of Physiology, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates

    M. Anwar Qureshi & F. Christopher Howarth

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  1. Holly Shiels
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  2. Anthony O’Connell
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  3. M. Anwar Qureshi
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  4. F. Christopher Howarth
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  5. Ed White
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  6. Sarah Calaghan
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Correspondence to Sarah Calaghan.

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Holly Shiels and Anthony O’Connell are equal first authorship.

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Shiels, H., O’Connell, A., Qureshi, M.A. et al. Stable microtubules contribute to cardiac dysfunction in the streptozotocin-induced model of type 1 diabetes in the rat. Mol Cell Biochem 294, 173–180 (2007). https://doi.org/10.1007/s11010-006-9257-9

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  • DOI: https://doi.org/10.1007/s11010-006-9257-9

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