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Effects of insulin on norepinephrine- and acetylcholine-induced membrane currents of pinealocytes from healthy Wistar and type 2 diabetic GK rats

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Abstract

The neurohormone melatonin is synthesized by the pineal gland under the stimulation of norepinephrine (NE). Its synthesis is inhibited by acetylcholine (ACh) and by insulin. Type 2 diabetic Goto Kakizaki (GK) rats have higher insulin and lower melatonin plasma levels than healthy Wistar rats. We investigate membrane potentials and currents of isolated pinealocytes in both rat strains and the influence of NE, ACh and insulin by using the perforated patch whole cell clamp technique. Pinealocyte membranes displayed a high resting Na+ conductance. Stimulation with NE further increased this Na+ conductance, which led to a slight depolarization in unclamped cells. The amplitude of the NE-evoked current was similar in both rat strains but the current fraction carried by Na+ was stronger in GK rats. Stimulation with ACh induced a transient inward current and depolarization. These effects were much more pronounced in the pinealocytes of GK rats. The NE-induced current, the ACh-induced current and the membrane depolarization were reduced by pre-administration of insulin in Wistar pinealocytes. Our results provide the first electrophysiological evidence for the modulation, by insulin, of the effects of NE and ACh in pinealocytes of normal rats. The pinealocytes of type 2 diabetic rats were not responsive to insulin. This might explain the reported correlation between the decreased insulin receptor mRNA transcript levels in GK rat pinealocytes and the lack of effect of insulin on ion channels in their cell membranes.

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Acknowledgements

The authors thank Prof. F. Dehghani for his helpful comments and Ms. Mühlbauer for linguistic assistance.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108, Halle/Saale, Germany

    Albrecht Klemenz & Elmar Peschke

  2. Saxon Academy of Sciences, Leipzig, Germany

    Sabine Wolgast, Renate Hanitzsch & Elmar Peschke

  3. Carl-Ludwig-Institute for Physiology, University of Leipzig, Leipzig, Germany

    Renate Hanitzsch

  4. Julius-Bernstein-Institute for Physiology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany

    Fritz Markwardt

Authors
  1. Albrecht Klemenz
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  2. Sabine Wolgast
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  3. Renate Hanitzsch
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  4. Fritz Markwardt
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  5. Elmar Peschke
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Correspondence to Albrecht Klemenz.

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This study was supported by the Saxon Academy of Sciences, Leipzig, Germany.

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Klemenz, A., Wolgast, S., Hanitzsch, R. et al. Effects of insulin on norepinephrine- and acetylcholine-induced membrane currents of pinealocytes from healthy Wistar and type 2 diabetic GK rats. Cell Tissue Res 355, 437–446 (2014). https://doi.org/10.1007/s00441-013-1748-x

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  • DOI: https://doi.org/10.1007/s00441-013-1748-x

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