Preferential elevation of protein kinase C isoform βII and diacylglycerol levels in the aorta and heart of diabetic rats: Differential reversibility to glycemic control by islet cell transplantation

Toyoshi Inoguchi, R. Battan, E. Handler, J. R. Sportsman, W. Heath, G. L. King

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    Abstract

    In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only α and βII PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, βII isoenzyme is preferentially increased in both aorta and heart, whereas PKC α did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague-Dawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications.

    Original languageEnglish
    Pages (from-to)11059-11063
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume89
    Issue number22
    DOIs
    Publication statusPublished - Nov 26 1992

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    Islets of Langerhans Transplantation
    Diglycerides
    Cell Transplantation
    Islets of Langerhans
    Protein Kinase C
    Aorta
    Protein Isoforms
    Streptozocin
    Inbred BB Rats
    Isoenzymes
    Diabetic Angiopathies
    Experimental Diabetes Mellitus
    Immunoblotting
    Hyperglycemia
    Smooth Muscle Myocytes
    Blood Vessels
    Sprague Dawley Rats
    Blood Glucose
    Transplants
    Glucose

    All Science Journal Classification (ASJC) codes

    • General

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    Preferential elevation of protein kinase C isoform βII and diacylglycerol levels in the aorta and heart of diabetic rats : Differential reversibility to glycemic control by islet cell transplantation. / Inoguchi, Toyoshi; Battan, R.; Handler, E.; Sportsman, J. R.; Heath, W.; King, G. L.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 22, 26.11.1992, p. 11059-11063.

    Research output: Contribution to journalArticle

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    abstract = "In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88{\%} and 40{\%} in the aorta and by 21{\%} and 72{\%} in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only α and βII PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, βII isoenzyme is preferentially increased in both aorta and heart, whereas PKC α did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague-Dawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications.",
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