Apoptotic Effect of Methylglyoxal in Pancreatic RINm5F Cells; Reversal by INGAP‐P

Abstract

Diabetes mellitus is a metabolic disease characterized by high level of blood sugar. In a healthy person, the hormone insulin from β‐cells of pancreatic islets regulates blood sugar level. In diabetic patients, there is a continuous loss of pancreatic β‐cells mass, dysfunction of β‐cells that result in deficiency of insulin. Methylglyoxal (MG), a normal by product of glycolysis, is in high in a diabetic person. MG causes oxidative stress to β‐cells leading to cell death. A linear pentadecapeptide segment of Islet Neogenesis Associated Protein ‐ Peptide (INGAP‐P), Ac‐IGLHDPSHGTLPNGS‐NH2, has been shown to induce proliferation of β‐cells through transdifferentiation of matured ductal cells. The goal of this research was to determine whether INGAP‐P protects RINm5F cells, an islet β‐cell line, from the detrimental effects of MG. Cells were treated with different concentrations of MG in the absence or presence of INGAP‐P. Cell viability of RINm5F cells after treatment was measured by MTT, [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide], assay at 570 nm. MG at 40μM caused 53% cell death in 24 hours. When treated with INGAP‐P at 1μM for 24 hours cell viability increased by 20%. When cells were treated with MG and INGAP‐P together, RINm5F cells showed no cell death suggesting that INGAP‐P protects the cells from MG. We are currently determining whether the cell death is due to apoptosis and how INGAP‐P protects RINm5F cells from the effect of MG. We will study the expression of Bax and Bcl2 in RINm5F cells treated with MG and INGAP‐P. The findings from this research will provide insights into the mode of action of INGAP‐P and guide the design of new synthetic drug molecules for diabetes that act in a similar mechanism.Support or Funding InformationUS Department of Education Title III GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.