Low insulin and high glucose induce abnormal relaxation in cultured
adult rat ventricular myocytes.
Davidoff, Amy J., and Jun Ren.
Program in Molecular and Cellular Cardiology, Department of
Internal Medicine, Wayne State University School of Medicine,
Detroit, MI 48201
APStracts 3:0294H, 1996.
One of the most prominent myocardial defects associated with diabetes
is abnormal diastole. We have recently reported that this dysfunction
involves prolonged relaxation (relengthening) in isolated ventricular
myocytes which occurs within days after induction of diabetes. The
current study was designed to evaluate the role of insulin and
glucose in the etiology of this dysfunction using a serum-free,
myocyte culture system. Adult rat ventricular myocytes were cultured
for 1-4 days in a "diabetic-like" medium containing 5 times
less insulin and 5 times more-glucose than in our normal medium.
Mechanical properties and Ca2+ transients (fura-2) were evaluated
using a high-resolution (120 Hz) video-based edge
detection\spectrofluormetric system. The cells were field stimulated
to contract at slow and physiologically relevant rates, and indices
of contraction and relaxation were evaluated. Relengthening was
markedly longer in myocytes cultured in low-insulin/high glucose
(LIHG) medium when compared to those in normal medium, while
contraction was unaffected. Intracellular Ca2+ transients showed
slower rates of decay in myocytes cultured in LIHG. These data
demonstrate that maintaining normal ventricular myocytes in a low
insulin/high glucose environment prolongs relaxation in a manner
similar to the effects of in vivo diabetes. Furthermore, the abnormal
relaxation is inducible in 1 day suggesting rapid alterations in
processes regulating relaxation, which likely include impaired Ca2+
sequestration and/or extrusion.
Received 3 April 1996; accepted in final form 24 June 1996.
APS Manuscript Number H305-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996