Protective effect of compound A (CpdA) on -cells in a gluco/lipotoxic microenvironment: initial evidence

ORELLANO, MS; SETULA, C; ARGANARAS, MILAGROS; PERONE, MJ; ANDREONE, L

Congreso; Reunion Anual de Sociedades de Biociencias (SAIC, SAB, AAFE, AACYTAL); 2023

Type 2 diabetes mellitus (T2DM) is a prevalent endocrine-metabolic disease characterized by hyperglycemia, peripheral insulin resistance and frequently linked to hyperlipidemia. Oxidative stress, coupled with the high demand for insulin leading to endoplasmic reticulum (ER) stress, contributes to dysfunction and death of pancreatic β-cells. We showed that Compound A (CpdA), a dissociative GR-ligand, mitigates oxidative and ER stress in β-cells under the inflammatory microenvironment of type 1 diabetes, improving their survival and function. We aimed to ascertain whether CpdA can also protect β-cells from the gluco/lipotoxic environment of T2DM. We used the rat β-cell line NS-1E. Gluco/lipotoxicity was induced with 30mM glucose and 100-500µM palmitate, and the effect of 10µM CpdA was evaluated. We analyzed nitric oxide (NO) by Griess, viability by MTT, mRNA by RT-qPCR and insulin by ELISA. GSIS (glucose-stimulated insulin secretion) index was calculated as the ratio of insulin released during 1h under stimuli of 20mM/2mM glucose.Results showed that exposure to 30mM glucose and 400µM palmitate (GLT) for 24h reduced viability by 50% (p