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Background <p>Solvents such as isopropyl alcohol (IPA, propan-2-ol, also called isopropanol) can occasionally be used for drug solubilization in in vitro screening of antidiabetic agents. However, their potential to interfere with pancreatic β-cell function remains poorly characterized.</p> Objective <p>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.</p> Methods <p>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 <i>N</i>-acetylcysteine (NAC, 2 mM) and quercetin (20 µM).</p> Results <p>IPA up to 1% (v/v) was non-cytotoxic in both cell lines. In MIN6 cells, IPA did not affect 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 it 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.</p> Conclusions <p>IPA can enhance insulin secretion in a cell-line-specific manner <i>via</i> 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.</p>

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Differential effects of isopropyl alcohol on glucose-induced insulin secretion in INS-1 and MIN6 cells

  • 期刊论文

  • 发表日期：

    2026年1月21日

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  • Valérie Pawlowski,
  • Valérie Plaisance,
  • Mathilde Lucas,
  • Emerson Giovanelli,
  • Chloé Derasse,
  • Alexandre Barras,
  • Amar Abderrahmani

摘要

Background

Solvents such as isopropyl alcohol (IPA, propan-2-ol, also called isopropanol) can occasionally be 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, 2 mM) and quercetin (20 µM).

Results

IPA up to 1% (v/v) was non-cytotoxic in both cell lines. In MIN6 cells, IPA did not affect 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 it 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.