Communication between the pancreas and liver, new molecular signals, and potential treatments by 2025

Adipocyte-derived exosomes carrying miR-138-5p may suppress insulin secretion and promote apoptosis in pancreatic beta-cells.

• The pancreas and liver are central metabolic hubs interconnected through neural and humoral pathways.
• Hepatic RNA demethylase ALKBH5 stabilizes glucagon receptor mRNA, which may activate lipogenic pathways and worsen hyperglycemia and fat accumulation in the liver.
• Colonic inflammation can activate hepatic signaling that is transmitted to the pancreas via the liver-pancreas vagus nerve circuit, potentially enhancing beta-cell proliferation during early obesity.
• Traditional pathogenic loops, such as pancreatic exocrine insufficiency and hepatic free fatty acid flux, may create a cycle of systemic inflammation and lipotoxicity affecting pancreatic beta-cells.
• Emerging interventions like GLP-1/GIP dual agonists and time-restricted feeding may represent promising strategies for obesity management.

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