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

ORELLANO MS; SÉTULA C; ARGAÑARÁS, M.; PERONE MJ; ANDREONE, L.

Mar del Plata.

Congreso; Reunion Anual de Sociedades de Biociencias; 2023

SAIC, SAB, AAFE, AACYTAL

Type 2 diabetes mellitus (T2DM) is a prevalent endocrine-metabolic disease characterizedby 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 thatCompound A (CpdA), a dissociative GR-ligand, mitigates oxidative and ER stress in β-cellsunder the inflammatory microenvironment of type 1 diabetes, improving their survival andfunction. We aimed to ascertain whether CpdA can also protect β-cells from thegluco/lipotoxic environment of T2DM.We used the rat β-cell line NS-1E. Gluco/lipotoxicity was induced with 30mM glucose and100-500μM 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 1hunder stimuli of 20mM/2mM glucose.Results showed that exposure to 30mM glucose and 400μM palmitate (GLT) for 24hreduced viability by 50% (p