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.

No abstract

No abstract

Selected parameters of cardiovascular function were evaluated in vitamin A-deficient rats at 70 days of age. Resting heart rate was increased by an average of 100 bpm (21.4+/-2.7%), whereas resting systolic blood pressure was normal in vitamin A-deficient animals. The maximal contractile force developed per milligram weight of tissue by aortic rings excised from vitamin A-deficient animals was reduced in response to high potassium (-25.0+/-8.7%) and phorbol 12,13-dibutyrate (-36.8+/-8.4%) but was only slightly reduced in response to norepinephrine (-17.8+/-11.1%). Intimal rubbing to remove the endothelium had no effect on the loss in contractile responsiveness, and the relaxant response to acetylcholine was similar between control and vitamin A-deficient tissue groups. This suggests that the decrease in contractility of vascular smooth muscle from the vitamin A-deficient rats did not involve altered release of endothelium-derived vasoactive factors. Western blot analysis suggested a reduction in the protein levels of several differentiation markers including alpha-actin (-22%), calponin (-37%), desmin (-37%), and vinculin (-40%), whereas the level of PKCalpha was unchanged from control values. Our findings indicate a significant decrease in contractile responsiveness of aortic smooth muscle of the vitamin A-deficient rat that may be associated with a down regulation in the expression of contractile-related proteins.