α-Adrenergic Stimulation Mediates Glucose Uptake Through Phosphatidylinositol 3-Kinase in Rat Heart

Author:

Doenst Torsten1,Taegtmeyer Heinrich1

Affiliation:

1. From the Department of Medicine, Division of Cardiology, University of Texas-Houston Medical School, Houston, Tex.

Abstract

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- 3 H]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 α-adrenergic stimulation), or isoproterenol (1 μmol/L) plus phentolamine (10 μmol/L, selective β-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 α- and β-adrenergic stimulation. Insulin and epinephrine, as well as selective α- and β-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; α-stimulation, 4.08±0.40; and β-stimulation, 3.72±0.34). Wortmannin completely inhibited insulin-stimulated and selective α-stimulated glucose uptake, but it did not affect the epinephrine-stimulated or selective β-stimulated glucose uptake. Sequential addition of insulin and epinephrine or insulin and α-selective stimulation showed additive effects on glucose uptake in both cases. Wortmannin further blocked the effects of insulin on glycogen synthesis. We conclude that α-adrenergic stimulation mediates glucose uptake in rat heart through a PI3-K–dependent pathway. However, the additive effects of α-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 α-adrenergic signaling cascade. The stimulating effects of both the α- and the β-adrenergic pathways on glucose uptake are independent of changes in cardiac performance.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

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