© 1999 American Heart Association, Inc.
Original Contribution |
-Adrenergic Stimulation Mediates Glucose Uptake Through Phosphatidylinositol 3-Kinase in Rat Heart
Presented in part at the 70th Annual Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–12, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-691).
From the Department of Medicine, Division of Cardiology, University of Texas-Houston Medical School, Houston, Tex.
Correspondence to Heinrich Taegtmeyer, MD, DPhil, Department of Internal Medicine, Division of Cardiology, University of Texas-Houston Medical School, 6431 Fannin, MSB 1.246, Houston, TX 77030. E-mail ht{at}heart.med.uth.tmc.edu
Abstract—We examined whether
insulin and catecholamines share common pathways for their
stimulating effects on glucose uptake. We perfused isolated working rat
hearts with Krebs-Henseleit buffer containing
[2-3H]glucose (5 mmol/L, 0.05 µCi/mL) and sodium
oleate (0.4 mmol/L). In the absence or presence of the
phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin
(3 µmol/L), we added insulin (1 mU/mL), epinephrine
(1 µmol/L), phenylephrine (100 µmol/L) plus
propranolol (10 µmol/L, selective 
-adrenergic
stimulation), or isoproterenol (1 µmol/L) plus
phentolamine (10 µmol/L, selective ß-adrenergic
stimulation) to the perfusate. Cardiac power was found to be
stable in all groups (between 8.07±0.68 and 10.7±0.88 mW) and
increased (25% to 47%) with addition of epinephrine, but not
with selective - and ß-adrenergic stimulation. Insulin and
epinephrine, as well as selective - and ß-receptor
stimulation, increased glucose uptake (the following values are in
µmol/[min · g dry weight]: basal, 1.19±0.13; insulin,
3.89±0.36; epinephrine, 3.46±0.27; -stimulation,
4.08±0.40; and ß-stimulation, 3.72±0.34). Wortmannin completely
inhibited insulin-stimulated and selective -stimulated glucose
uptake, but it did not affect the epinephrine-stimulated or
selective ß-stimulated glucose uptake. Sequential addition of insulin
and epinephrine or insulin and -selective stimulation showed
additive effects on glucose uptake in both cases. Wortmannin further
blocked the effects of insulin on glycogen synthesis. We conclude that
-adrenergic stimulation mediates glucose uptake in rat heart through
a PI3-K–dependent pathway. However, the additive effects of
-adrenergic stimulation and insulin suggest 2 different isoforms of
PI3-K, compartmentation of PI3-K, potentiation, or inhibition by
wortmannin of another intermediate of the -adrenergic signaling
cascade. The stimulating effects of both the - and the
ß-adrenergic pathways on glucose uptake are independent of changes in
cardiac performance.
Key Words: isolated working rat heart • wortmannin • glucose tracer • signal transduction
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