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Exploring levels of hexosamine biosynthesis pathway intermediates and protein kinase C isoforms in muscle and fat tissue of zucker diabetic fatty rats

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Abstract

Many studies suggest that insulin resistance develops and/or is maintained by an increased flux of glucose through the hexosamine biosynthesis pathway. This pathway may attenuate insulin-stimulated glucose uptake by activating protein kinase C (PKC). Therefore, we investigated whether the concentrations of the major hexosamine metabolites, uridine diphosphate-N-acetyl-glucosamine (UDP-GlcNAc) and uridine diphosphate-N-acetyl-galactosamine (UDP-GalNAc), and the expression levels of PKC isoforms were affected in Zucker Diabetic Fatty (ZDF) rats, an animal model widely used to study type 2 diabetes mellitus. At the age of 6 wk, control and ZDF rats were normoglycemic. Whereas control rats remained normoglycemic, the ZDF rats became hyperglycemic. The amount of UDP-GlcNAc and UDP-GalNAc in muscle tissue of ZDF rats was similar at 6, 12, 18, and 24 wk of age. Moreover, the concentration of both hexosamines did not differ among ZDF, phlorizin-treated ZDF, and control rats. Western blot analysis revealed that PKCα, δ, ɛ, and ζ, but not PKCβ and γ, were expressed in muscle and fat tissues from 6- and 24-wk-old control and ZDF rats. In addition, we did not observe changes in the expression levels of the PKC isoforms following prolonged hyperglycemia. Taken together, these findings indicate that the amounts of several metabolites from the hexosamine biosynthesis pathway and PKC isoforms, both hypothesized to be important in the development and/or maintenance of the insulin-resistant state of muscle and fat tissue, are not different in ZDF compared with nondiabetic rats.

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Authors and Affiliations

  1. Department of Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands

    Remko R. Bosch, Susan W. J. Janssen & Ad R. M. M. Hermus

  2. Department of Biochemistry, University Medical Centre Nijmegen, Nijmegen, The Netherlands

    Sjenet E. van Emst-de Vries & Peter H. G. M. Willems

  3. Department of Animal Physiology, Faculty of Science, University of Nijmegen, Nijmegen, The Netherlands

    Susan W. J. Janssen & Gerard J. M. Martens

  4. Department of Chemical Endocrinology, University Medical Centre Nijmegen, PO Box 9101, NL-6500 HB, Nijmegen, The Netherlands

    Remko R. Bosch, Paul N. Span, André J. Olthaar & C. G. J. (Fred) Sweep

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  1. Remko R. Bosch
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  2. Susan W. J. Janssen
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  3. Paul N. Span
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  4. André J. Olthaar
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  5. Sjenet E. van Emst-de Vries
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  6. Peter H. G. M. Willems
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  8. Ad R. M. M. Hermus
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  9. C. G. J. (Fred) Sweep
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Correspondence to Remko R. Bosch.

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Bosch, R.R., Janssen, S.W.J., Span, P.N. et al. Exploring levels of hexosamine biosynthesis pathway intermediates and protein kinase C isoforms in muscle and fat tissue of zucker diabetic fatty rats. Endocr 20, 247–252 (2003). https://doi.org/10.1385/ENDO:20:3:247

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  • DOI: https://doi.org/10.1385/ENDO:20:3:247

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