Ghrelin Protects Pancreatic Beta-Cells from Diabetes-Related Damage

Pancreatic β-cells are vital for producing insulin, the hormone that regulates blood sugar. In conditions like type 2 diabetes (T2D), these cells suffer from glucolipotoxicity (damage caused by high glucose and lipid levels), leading to β-cell dysfunction and apoptosis (programmed cell death). This damage is often linked to endoplasmic reticulum (ER) stress, particularly through the IRE1/JNK pathway. This study aimed to determine if ghrelin, a hunger-stimulating hormone, could protect β-cells from glucolipotoxicity-induced damage by modulating ER stress.

Ghrelin treatment demonstrated a significant protective effect on pancreatic β-cells exposed to glucolipotoxicity. Specifically, β-cell viability was notably improved by approximately 28% compared to untreated glucolipotoxic cells. Furthermore, markers of apoptosis were substantially reduced, with caspase-3 activity decreasing by a remarkable 42% in ghrelin-treated cells. The functional capacity of β-cells also improved, as evidenced by a 2.1-fold increase in glucose-stimulated insulin secretion. Crucially, ghrelin achieved these protective effects by suppressing the activation of the endoplasmic reticulum (ER) stress-induced IRE1/JNK pathway, showing a 58% reduction in JNK phosphorylation and a 35% decrease in IRE1α expression. This indicates a direct mechanistic intervention.