Insulin-stimulated glucose transport is dependent on Golgi function in isolated working rat heart

Insulin and epinephrine stimulate glucose uptake through distinct mechanisms. We tested the hypothesis that the golgi apparatus is involved in insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation.

We perfused isolated working rat hearts with Krebs-Henseleit buffer containing [2-(3)H]glucose (5 mmol/l, 0.05 microCi/ml) and Na-oleate (0.4 mmol/l). In the absence or presence of the inhibitor of golgi function, brefeldin A (30 micromol/l), either insulin (1 mU/ml), epinephrine (1 micromol/l), or phenylephrine (100 micromol/l) plus propranolol (10 micromol/l, selective alpha -adrenergic stimulation) were added to the perfusate.

Cardiac power was stable in all groups (between 8.56+/-0.61 and 10.4+/-1.11 mW) and increased (34%) with addition of epinephrine, but not with selective alpha -adrenergic stimulation. Insulin, epinephrine, and selective alpha -receptor stimulation increased glucose transport and phosphorylation (micromol/min/g dry wt, basal: 1.19+/-0.13, insulin: 3.89+/-0.36, epinephrine: 3.46+/-0.27, alpha -stimulation: 4.08+/-0.40). Brefeldin A increased basal glucose transport and phosphorylation and blunted insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Selective alpha -stimulated glucose transport and phosphorylation was also blunted by brefeldin A.

Both insulin and alpha -adrenergic stimulation result in glucose transporter translocation from a pool that requires golgi function. Stimulation with epinephrine results in glucose transporter translocation from a pool that does not require golgi function. The stimulating effects of the alpha -adrenergic pathway on glucose transport and phosphorylation are independent of changes in cardiac performance.