In previous studies using perifused collagenase-isolated rat islets, retinol (vit A) inhibited glucose-induced Diphasic insulin release and glucose oxidation. To further evaluate vit A action and elucidate cellular mechanisms of insulin release, we tested the effects of vit A on glucose uptake by islets, on other stimuli of insulin release, and oh islet ultrastructure and the effects of calcium on vit A inhibition of insulin release. Vit A did hot inhibit 2-deoxy-D-glucose uptake into islets. Vit A inhibited second phase 9.7 and 13.9 mM glucoseinduced insulin release to 50%, 10 mM glyceraldehydeinduced release to 64%, and 20 mM leucine-induced release to 66% of control. First phase, release was unaffected. Kinetic analysis of the effects of vit A on glucose-induced release indicated a change in the Vmax but not in the Km, suggesting inhibition of a potentiator of insulin release by vit A. Calcium (4 mM) opposed vit A inhibition of glucose-induced release.
Ultrastructurally, vit A decreased the volume fraction of secretory granules to 90% of control, increased the volume fraction of material within the rough endoplasmic reticulum to 147% of control, and increased the outer and decreased the inner mitochondrial compartment volume fractions by 14%.
Our functional and ultrastructural findings, in all, suggest that vit A inhibitioh of second phase insulin release is not specific for glucose and may be mediated in part through impairment of mitochondrial function and intracellular glucose oxidation.
