Elucidating the association of vitamin A and of diabetes: A clinical and molecular study
By: Jalal Taneera
College of Medicine - Sharjah institute for medical research, University of Sharjah
Date/Time: Tuesday, September 14, 2021 at 2:30 PM
Venue: MS Teams
Type 2 diabetes (T2D) is a complex polygenic disease with unclear mechanisms. Clinical studies on the association of vitamin A with T2D in humans are still controversial. Also, whether ablation of VA receptors is involved in pancreatic β-cell dysfunction is not mature.
Herein, we investigated the plasma levels of vitamin A and its correlations with clinical phenotypes in Emirati population cohort comprised of 158 T2D-subjects and 90 healthy controls. The effect of glucose-and lipid-lowering medications on vitamin A levels was also studied. RNA-sequencing from human islets with/without type 2 diabetes (T2D) were utilized to profile the expression of VA-regulatory genes. Several functional studies in rat INS-1 cells will be performed, including siRNA silencing of VA receptors to assess their effect on insulin secretion, glucose uptake, expression of key proteins involved in β-cell function, cell survival and viability
Serum levels of vitamin A were significantly lower in T2D-subjects than healthy control (p < 0.01). Vitamin A levels were unaffected by gender base and inversely correlated with age, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), waist circumference, triglycerides, and body mass index (BMI). Regression analysis revealed that HbA1c and age are predictors for vitamin A. Intake of glucose- or lipid-lowering medications showed no effect on vitamin A levels.
Microarray and RNA-sequencing expression analysis showed RARα, β and γ are expressed in human pancreatic islets. A significant reduction (p=0.004) of RARβ in diabetic/hyperglycemic donors (HbA1c ≥ 6.3%) compared to nondiabetic (HbA1c < 6%). Expression silencing of Rarβ in INS-1 cells impaired glucose-stimulated insulin secretion (GSIS) without affecting cell viability or apoptosis. Interestingly, reactive oxygen species (ROS) production levels were elevated and glucose uptake was reduced in Rarβ-silenced cells. More, mRNA and protein expression of Insulin 1(Ins1), Pdx1, Neurod1, Mafa, Snap25, Vamp2, Insr and Gck was downregulated in Rarβ-silenced cells, whereas Glut2 was up-regulated.
In conclusion, vitamin A is reduced among Emirati-T2D subjects with no influence of glucose and lipid-lowering medications. RARβ influences insulin secretion and pancreatic β-cell function. Our data further support the potential role of vitamin A in the development of T2D.