Vitamin A deficiency impairs fetal islet development and causes subsequent glucose intolerance in adult rats.
To determine the role of vitamin A in fetal islet development, beta- and alpha-cell mass, apoptosis, and alpha- and beta-cell replication were measured in rats using a model of marginal vitamin A deficiency. Female rats before and during pregnancy and their offspring postweaning were fed a diet containing retinol as retinyl palmitate at a low marginal (LM, 0.25 mg/kg diet) or a sufficient (SUFF, 4.0 mg/kg diet) level. Fetal islet size, replication, apoptosis, and offspring glucose tolerance were examined. Both beta-cell area and number per islet were reduced approximately 50% in fetuses from dams fed an LM vitamin A diet compared with those from dams fed the SUFF vitamin A diet. The alpha-cell area and number per fetal islet were not affected by vitamin A deficiency. Apoptosis was not increased. The percentage of newly replicated beta-cells in the LM fetal pancreas was 42% less than that of SUFF offspring, but alpha-cell replication was not affected. To determine whether this decrease in beta-cell area affected adult glucose tolerance and insulin secretion, 65-d-old offspring were subject to glucose tolerance tests. LM rats had a 55% lower plasma insulin level and a 76% higher serum glucose than SUFF rats. The same pattern could be seen in 35-d-old rats. These findings show that vitamin A deficiency decreases beta-cell mass and this reduction can be attributed to a reduced rate of fetal beta-cell replication in LM offspring. This may contribute to impaired glucose tolerance later in adult life.
Matthews
Kimberly A
KA
Department of Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
Rhoten
William B
WB
Driscoll
Henry K
HK
Chertow
Bruce S
BS
D000818:Animals; D001786:Blood Glucose; D004032:Diet; D005314:Embryonic and Fetal Development; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014802:Vitamin A Deficiency / Q000150:complications*
D001786:Blood Glucose; D007328:Insulin