Exploring levels of hexosamine biosynthesis pathway intermediates and protein kinase C isoforms in muscle and fat tissue of Zucker Diabetic Fatty rats.
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 PKCalpha, delta, epsilon, andzeta, but not PKCbeta and gamma, 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.
Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. R.Bosch@ace.umcn.nl
Remko R
RR
Bosch
Susan W J
SW
Janssen
Paul N
PN
Span
André
A
Olthaar
Sjenet E
SE
van Emst-de Vries
Peter H G M
PH
Willems
Gerard
G
Martens J M
Ad R M M
AR
Hermus
C C J
CC
Sweep
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006595:Hexosamines / Q000096:biosynthesis*; D007328:Insulin / Q000097:blood; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D010695:Phlorhizin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000378:metabolism; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D001786:Blood Glucose; D006595:Hexosamines; D007328:Insulin; D007527:Isoenzymes; D009711:Nucleotides; D014537:Uridine Diphosphate N-Acetylglucosamine; D014536:Uridine Diphosphate N-Acetylgalactosamine; D010695:Phlorhizin; D011493:Protein Kinase C