Disruption of Islet β-Cells Integrity via TNF-α Activated Apoptotic Signalling in Acute Pancreatitis

Tumor necrosis factor alpha (TNF-α) serves as a major regulator of inflammatory responses. The initial, critical release and activation of TNF-α in acute pancreatitis (AP) is primarily triggered within the pancreatic acinar cells through intracellular mechanisms in response to initial injury. This local, acinar cell-derived TNF-α recruits immune cells into the pancreas, which then produce more TNF-α, leading to the amplification of the inflammatory cascade. This opinion emphasises the role of TNF-α-mediated dysfunction of pancreatic β-cells and apoptosis induction through the Bax/Bcl-2/caspase-3 pathway. AP is often diagnosed by autodigestive pancreatic damage and systemic inflammatory response with transient or persistent hyperglycaemia. TNF-α signalling takes place through TNFR1, which initiates apoptotic events that weaken mitochondrial integrity leading to β-cell disruption and diminished insulin secretion. Studies reported TNF-α-mediated increases in Bax expression, anti-apoptotic Bcl-2 suppression and activation of caspase-3. Therapeutic strategies such as TNFR1 inhibitors, Bax/Bcl-2 modulators and BH3 mimetics possess great potential to preserve β-cell integrity. However, TNF-α inhibition requires a careful approach in order to avoid compromising immune defence in AP patients. TNF-α-driven β-cell apoptosis represents a strong link between inflammation and metabolic dysfunction that makes it a suitable target for AP. Future directions should prioritise translational research in human cohorts and developing receptor-specific interventions to balance immune modulation with β-cell preservation.