EFFECTS OF VITAMIN-A-DEFICIENCY AND REPLETION ON RAT GLUCAGON-SECRETION

To determine whether vitamin A is involved in pancreatic alpha cell fu nction, we tested for (a) effects of vitamin A deficiency on glucagon release from perifused islets and perfused pancreases, and (b) the pre sence of cytosolic retinol-binding proteins (CRBP) and retinoic acid-b inding proteins (CRABP), in the glucagon secreting a cell line, 1n-R1- G9. Arginine 19 mM plus glucose 2.8 mM-stimulated glucagon secretion w as markedly impaired in islets and pancreases of vitamin A-deficient r ats or rats that had at some time been cycled through vitamin A defici ency (ever A-def) despite repletion with retinoids for 2-4 weeks. Insu lin secretion was impaired likewise. Repletion starting early in the d evelopment of vitamin A deficiency and for a longer period of time (18 or 60 days) did not restore glucagon secretion, but did normalize ins ulin secretion. CRBP and CRABP were present in 1n-R1-G9 cells. We conc lude that (a) vitamin A deficiency is associated with a defect in gluc agon secretion; (b) The defect in secretion occurs early in the course of vitamin A deficiency; (c) The defect persists despite repletion; a nd (d) The requirement of vitamin A for secretion and the presence of CRBP and CRABP in glucagon-secreting cells support a physiologic role for vitamin A at the or cell level.