Differential Effects of Isopropyl Alcohol on Glucose-Induced Insulin Secretion in INS-1 and MIN6 Cells

Background Solvents such as isopropyl alcohol (IPA, propan-2-ol also called isopropanol) are commonly used for drug solubilization in in vitro screening of antidiabetic agents. However, their potential to interfere with pancreatic β-cell function remains poorly characterized. Objective This study aimed to assess the effects of IPA on insulin secretion and viability in two widely used β-cell models, INS-1 and MIN6. Methods INS-1 and MIN6 cells were exposed to increasing concentrations of IPA (0–10% v/v). Cell viability, total insulin content, and glucose-stimulated insulin secretion (GSIS) were evaluated. Mechanistic insights were investigated using co-incubation with the K(ATP) channel opener diazoxide (200 µM), the protein kinase A (PKA) inhibitor H89 (10 µM), and antioxidants N -acetylcysteine (NAC, 5 mM) and quercetin (20 µM). Results IPA up to 1% (v/v) was non-cytotoxic in both cell lines. In MIN6 cells, IPA had no effect on GSIS. In contrast, IPA dose-dependently enhanced GSIS in INS-1 cells, without altering basal secretion or total insulin content. This effect was unaffected by NAC or quercetin but was abolished by diazoxide and significantly reduced by H89, suggesting a mechanism involving K(ATP) channel closure, protein kinase A (PKA) activation and its downstream signaling. However, intracellular cAMP levels remained unchanged, indicating a cAMP-independent activation of PKA. Conclusions IPA can enhance insulin secretion in a cell-line-specific manner via PKA-dependent, cAMP-independent pathways involving K(ATP) channels. These findings underscore the importance of solvent choice in drug screening, as IPA may confound β-cell functional assays.