Vitamin A deficiency impairs fetal islet development and causes subsequent glucose intolerance in adult rats

Abstract

To determine the role of vitamin A in fetal islet development, β- and α-cell mass, apoptosis, and α- and β-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 β-cell area and number per islet were reduced ∼50% in fetuses from dams fed an LM vitamin A diet compared with those from dams fed the SUFF vitamin A diet. The α-cell area and number per fetal islet were not affected by vitamin A deficiency. Apoptosis was not increased. The percentage of newly replicated β-cells in the LM fetal pancreas was 42% less than that of SUFF offspring, but α-cell replication was not affected. To determine whether this decrease in β-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 β-cell mass and this reduction can be attributed to a reduced rate of fetal β-cell replication in LM offspring. This may contribute to impaired glucose tolerance later in adult life.