The Impact of Psilocybin on High Glucose/Lipid-Induced Changes in INS-1 Cell Viability and Dedifferentiation

Psilocybin, a compound from Psilocybe mushrooms that activates serotonin receptors, may protect insulin-producing β-cells from damage caused by high glucose and high lipid conditions. In experiments with rat insulinoma cells, psilocybin pretreatment reduced cell loss, likely by altering apoptotic biomarkers and reducing phosphorylation of TXNIP, STAT-1, and STAT-3. It also modulated expression of genes linked to β-cell dedifferentiation, such as Pou5f1 and Nanog, suggesting it could help maintain β-cell identity. These findings indicate potential for psilocybin in treating Type II diabetes, though further research is needed.

Study at a glance

Abstract

Serotonin emerges as a pivotal factor influencing the growth and functionality of β-cells. Psilocybin, a natural compound derived from mushrooms of the Psilocybe genus, exerts agonistic effects on the serotonin 5-HT2A and 5-HT2B receptors, thereby mimicking serotonin’s behavior. This study investigates the potential impacts of psilocybin on β-cell viability, dedifferentiation, and function using an in vitro system. The INS-1 832/13 Rat Insulinoma cell line underwent psilocybin pretreatment, followed by exposure to high glucose-high lipid (HG-HL) conditions for specific time periods. After being harvested from treated cells, total transcript and cellular protein were utilized for further investigation. Our findings implied that psilocybin administration effectively mitigates HG-HL-stimulated β-cell loss, potentially mediated through the modulation of apoptotic biomarkers, which is possibly related to the mitigation of TXNIP, STAT-1, and STAT-3 phosphorylation. Furthermore, psilocybin exhibits the capacity to modulate the expression of key genes associated with β-cell dedifferentiation, including Pou5f1 and Nanog, indicating its potential in attenuating β-cell dedifferentiation. This research lays the groundwork for further exploration into the therapeutic potential of psilocybin in Type II diabetes intervention.