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, 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.

Anti-diabetic action of all-trans retinoic acid and the orphan G protein coupled receptor GPRC5C in pancreatic β-cells

“…The output reads were aligned to the human reference genome (hg19) with STAR [18,19] and feature counting was done using feature Counts [20]. Raw data was normalised using trimmed mean of M-values and presented as Fragments Per Kilobase of Exon Per Million Fragments Mapped (FPKM) or transformed using into log2 counts per million using the voom-function secretion during acute exposure (<1 h) suggests that it also signals via a non-genomic mechanism that is independent of transcriptional regulation induced by nuclear retinoid acid receptors [11][12][13].…”

Identification of 9- cis -retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion

“…Also uncertain is the contribution of impaired glucose tolerance to diminished pancreatic β-cell function and mass associated with type 2 diabetes (5). GSIS relies on the pancreas, and pancreas development, islet formation, and function require normal vitamin A nutriture (6)(7)(8). Vitamin A restriction during development impairs islet development and promotes glucose intolerance in adult rodents.…”

“…On the other hand, restricting vitamin A in mature diabetes-prone rats reduces diabetes and insulitis, possibly through enhancing glucose sensing and metabolism. Alltrans-retinoic acid (atRA), an activated metabolite of vitamin A, regulates pancreas development, and atRA does not enhance the incidence of diabetes in diabetes-prone rats fed a vitamin Adeficient diet (7,9,10). Although the contribution of vitamin A to pancreas development through atRA seems clear, mechanisms whereby vitamin A affects mature pancreas function have not been determined in depth, nor have the specific vitamin A metabolites been identified that contribute to GSIS control.…”

Evidence-based and heuristic approaches for customization of care in cardiometabolic syndrome after spinal cord injury

“…These are summarized in Micronutrient status may also be suboptimal in the acute phase of recovery from injury, but improve over time. 55 Almost all of the above listed micronutrients have been linked to glycemic and/or lipid profiles, [58][59][60][61][62][63][64][65][66][67][68][69][70][71] but a detailed exploration of these deficiencies and their association with CMS risks of dysglycemia and dyslipidemia exceeds the scope of this monograph. In addition, only a few of these deficiencies have consistently been reported to be prevalent in persons with SCI over the last 10 years.…”