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.
Department of Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
Kimberly A
KA
Matthews
William B
WB
Rhoten
Henry K
HK
Driscoll
Bruce S
BS
Chertow
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