Effects of vitamin A deficiency and repletion on rat glucagon secretion.
To determine whether vitamin A is involved in pancreatic alpha cell function, we tested for (a) effects of vitamin A deficiency on glucagon release from perifused islets and perfused pancreases, and (b) the presence of cytosolic retinol-binding proteins (CRBP) and retinoic acid-binding proteins (CRABP), in the glucagon-secreting alpha cell line, ln-R1-G9. Arginine 19 mM plus glucose 2.8 mM-stimulated glucagon secretion was markedly impaired in islets and pancreases of vitamin A-deficient rats or rats that had at some time been cycled through vitamin A deficiency (ever A-def) despite repletion with retinoids for 2-4 weeks. Insulin secretion was impaired likewise. Repletion starting early in the development of vitamin A deficiency and for a longer period of time (18 or 60 days) did not restore glucagon secretion, but did normalize insulin secretion. CRBP and CRABP were present in ln-R1-G9 cells. We conclude that (a) vitamin A deficiency is associated with a defect in glucagon secretion; (b) The defect in secretion occurs early in the course of vitamin A deficiency; (c) The defect persists despite repletion; and (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 alpha cell level.
Chertow
B S
BS
Medical Service, VA Medical Center, Huntington, West Virginia.
Driscoll
H K
HK
Blaner
W S
WS
Meda
P
P
Cordle
M B
MB
Matthews
K A
KA
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D004224:Diterpenes; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000032:analysis; D012176:Retinoids / Q000494:pharmacology*; D012177:Retinol-Binding Proteins / Q000032:analysis; D054840:Retinol-Binding Proteins, Cellular; D000084562:Retinyl Esters; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D004224:Diterpenes; D007328:Insulin; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin; D005934:Glucagon; D001120:Arginine; D005947:Glucose