Low Glucose Increases Oxidative Stress and Impacts GSIS (Glucose Stimulated Insulin Secretion) in INS-1 Cells and Rat Islets.

Oxidative stress plays an important role in tissue damage by hyperglycemia and hypoglycemia. It is well known that chronic exposure to hyperglycemia can lead to cellular dysfunction via oxidative stress and them are decreases in antioxidant enzymes in pancreatic β cells exposured to high glucose condition. As hyperglycemia worsens, the β cell steadily undergoes deterioration, secretes less and less insulin, and becomes a participant in a downward spiral of loss of function. However, little is known about correlation of oxidative stress with hypoglycemia in pancreatic β cells yet. To investigate the effect of hypoglycemia (obtained by low glucose media) on islets, we analyzed intracellular peroxide levels, insulin mRNA levels, PDX-1, MafA, mitochondrial function (intracellular ATP level) and GSIS in INS-1 cells and rat islets after culture at low glucose (2 mM) condition. The intracellular peroxide levels of the pancreatic islets (INS-1 cells, rat islets) measured by flow cytometry were increased in not only the high glucose (30 mM glucose in INS-1 cell or 50 mM ribose in rat islets) media but also low glucose media (2 mM) compared to 5.6 mM glucose media (p<0.05). The insulin mRNA levels, PDX-1, MafA, and GSIS were also decreased in both high and low glucose media compared to 5.6 mM glucose media (p<0.05). Also, the intracellular ATP level decreased in low glucose media compared to 5.6 mM glucose media (p<0.05). These results suggest that the β cell dysfunction of low glucose conditions is mainly due to ROS accumulation in INS-1 cells and rat islets, which is similar with glucose toxicity. [ABSTRACT FROM AUTHOR]