CELLULAR MECHANISMS OF INSULIN RELEASE - EFFECTS OF RETINOL ON INSULIN RELEASE AND ISLET ULTRASTRUCTURE

In previous studies using perifused collagenase-isolated rat islets, retinol (vit [vitamin] A) inhibited glucose-induced biphasic insulin release and glucose oxidation. The effects of vit A were tested on glucose uptake by islets, on other stimuli of insulin release, and on islet ultrastructure; the effects of Ca on vit A inhibition of insulin release were also studied. Vit A did not inhibit 2-deoxy-D-glucose uptake into islets. Vit A inhibited 2nd phase 9.7 and 13.9 mM glucose-induced insulin release to 50%, 10 mM glyceraldehyde-induced release to 64% and 20 mM Leu-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. Ca (4 mM) opposed vit A inhibition of glucose-induced release. Ultrastructurally, vit A decreased the volume fraction of secretory granules to 80% 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%. Vit A inhibition of 2nd phase insulin release is apparently not specific for glucose and may be mediated in part through impairment of mitochondrial function and intracellular glucose oxidation.