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Protein Kinase C Plays an Important Role in Exaggerated Vasoconstriction Associated with Insulin Deficiency but not Resistance

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Proceedings of the National Academy of Sciences, India Section B: Biological Sciences Aims and scope Submit manuscript

Abstract

Deteriorated vascular reactivity has critical role in diabetic vascular complications. In the present study, the role of PKC on diabetes-induced deteriorated vascular reactivity was investigated. Insulin deficiency was induced by streptozotocin while its resistance by administering 10 % fructose. Isolated thoracic aorta reactivity to phenylephrine, KCl, acetylcholine and sodium nitroprusside was studied. The effects of in vitro incubation with the protein kinase C stimulant, phorbol 12-myristate 13-acetate or inhibitor, chelerythrine were also studied. Insulin deficiency increased responses to phenylephrine and KCl, decreased response to acetylcholine but showed no response to sodium nitroprusside. In vitro incubation with chelerythrine (7 µM, 20 min) normalized responses to KCl and phenylephrine but did not change response to acetylcholine or SNP. On the other hand, insulin resistance increased response to phenylephrine and KCl, impaired response to acetylcholine but did not affect the response to sodium nitroprusside, while in vitro incubation with chelerythrine did not change responses to phenylephrine, KCl, acetylcholine or sodium nitroprusside. In addition, protein kinase C stimulation by incubation of isolated normal aorta with different concentrations of phorbol 12-myristate 13-acetate (200, 400, 800 nM) for 1 h led to a similar impairment in isolated normal aorta to that in case of ID while co-incubation with chelerythrine restored normal vascular responses to KCl and phenylephrine. In conclusion, inhibition of protein kinase C by chelerythrine protects from the exaggerated vasoconstriction associated with insulin deficiency but not the resistance.

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Abbreviations

ANOVA:

Analysis of variance

IR:

Insulin resistance

NO:

Nitric oxide

PE:

Phenylephrine

SNP:

Sodium nitroprusside

PMA:

Phorbol 12-myristate 13-acetate

PKC:

Protein kinase C

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Acknowledgments

The study is supported by a research fund from the Egyptian Ministry for Higher Education funding agency; Science and Technology Development (STDF, www.stdf.org.eg), Fund, ID 1024.

Conflict of interest

There is no conflict of interest in publication of the paper.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah, 21589, Kingdom of Saudi Arabia

    Hany M. El-Bassossy

  2. Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    Hany M. El-Bassossy, Nora Desoky & Ahmed Fahmy

Authors
  1. Hany M. El-Bassossy
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  2. Nora Desoky
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  3. Ahmed Fahmy
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Correspondence to Hany M. El-Bassossy.

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El-Bassossy, H.M., Desoky, N. & Fahmy, A. Protein Kinase C Plays an Important Role in Exaggerated Vasoconstriction Associated with Insulin Deficiency but not Resistance. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 85, 807–814 (2015). https://doi.org/10.1007/s40011-014-0479-4

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  • DOI: https://doi.org/10.1007/s40011-014-0479-4

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