Insulin-associated changes in carnitine palmitoyltransferase
activity are mediated through the insulin-like growth factor i
pathway in the cultured neonatal rat cardiac myocyte.
Hudson, Edgar K., Dachun Wang, Loren L. Bieber, L. Maximilian Buja,
and Jeanie B. McMillin.
The Department of Pathology and Laboratory Medicine, The University
of Texas Medical School at Houston, The University of Texas Health
Science Center, 6431 Fannin, Houston, Texas 77030
APStracts 3:0007H, 1996.
The mitochondrial carnitine palmitoyltransferase (CPT) system is
composed of two proteins, CPT-I and CPT-II, which, together with the
carnitine acylcarnitine translocase, are involved in the transport of
fatty acids into the mitochondrial matrix for [beta]-oxidation. In
the liver, CPT-I and its inhibition by malonyl-CoA are sensitive to
hormonal (10 -9M) levels of insulin; however, a similar effect of
insulin on heart CPT is controversial. In cultured neonatal rat
cardiac myocytes, tissue culture concentrations (1.7 [mu]M) of
insulin increase CPT and cytochrome oxidase activities as well as
mitochondrial protein synthesis, suggesting that a growth mechanism
may be involved. Since at high concentrations, insulin may interact
with the insulin-like growth factor (IGF-I) receptor, the
consequences of insulin's action on heart cells in culture may be
mediated through the IGF pathway. Consistent with an IGF-mediated
pathway for the effect of insulin, incorporation of radioactivity
into immunoprecipitated CPT-II from insulin-treated cardiac myocytes
is dramatically increased over control cells. The amount of
immunoreactive CPT-I is also increased in insulin-treated cells.
Moreover, an IGF-I analogue which inhibits the autophosphorylation of
the IGF-I receptor blunts the insulin-mediated increase in CPT-I and
-II activities by greater than 70%. At low, physiologically relevant
concentrations (10 ng/ml) IGF-I significantly increases the
activities of both CPT-I and -II, and the IGF-I analogue eliminates
the IGF-I response. This is the first study to suggest involvement of
the IGF-I pathway in the regulation of mitochondrial CPT synthesis
and activities in the heart.
Received 5 September 1995; accepted in final form 8 December
1995.
APS Manuscript Number H839-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96