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Insulin's effect on protein kinase C and diacylglycerol induced by diabetes and glucose in vascular tissues
Ist Teil von
American journal of physiology: endocrinology and metabolism, 1994-09, Vol.267 (3), p.E369-E379
Ort / Verlag
United States
Erscheinungsjahr
1994
Quelle
MEDLINE
Beschreibungen/Notizen
T. Inoguchi, P. Xia, M. Kunisaki, S. Higashi, E. P. Feener and G. L. King
Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Boston, Massachusetts 02215.
We have reported that membranous protein kinase C (PKC) activities and
total diacylglycerol (DAG) levels are increased in the heart and aorta of
diabetic rats, which cannot be easily reversed by euglycemic control.
However, insulin treatment, which achieved euglycemia, can prevent the
increase in PKC activities and DAG levels. Chronic exposure to elevated
glucose levels (5.5 vs. 22 mM) increased DAG levels in cultured bovine and
rat aortic endothelial cells and smooth muscle cells by 31, 140, and 143%,
respectively, only after 3 days of incubation. Glyceraldehyde, which can
stimulate the de novo synthesis of DAG, significantly increased DAG levels
by 7.1 +/- 0.6-fold after only 16 h of incubation. Elevated glucose levels
did not affect labeled DAG when all of the vascular cells were incubated
with [3H]arachidonate, [3H]glycerol, or [3H]phosphatidylcholine, whereas
[3H]palmitate- and [3H]oleic acid-labeled DAG levels were significantly
increased, indicating that the glucose-stimulated increase in DAG is
derived partially from the de novo synthesis pathway. Immunoblotting
studies showed increases only in PKC isoform beta II but not alpha in
aortic smooth muscle cells. The phosphorylation level of MARCKS protein, an
intracellular substrate of PKC, was also increased, consistent with the PKC
activity increase. These findings showed that diabetic and
hyperglycemia-induced increases in PKC activity and DAG levels in the heart
and aorta are preventable by insulin treatment.