Dimethyl sulfoxide acutely enhances regulated insulin secretion in the MIN6-K8 mouse insulinoma cell line

Abstract

Diabetes mellitus is a metabolic disorder projected to afflict 700 million people globally by 2045. Fundamental to the progression of diabetes is an insufficient supply of insulin to meet metabolic demand. The MIN6-K8 cell line is a mouse insulinoma model of pancreatic β-cells frequently used to study the mechanisms of insulin secretion. Here, we evaluated the effects of short-term exposure to dimethyl sulfoxide (DMSO), a polar aprotic solvent commonly used in drug screening, on physiological characteristics of MIN6-K8 cells. Short-term exposure of MIN6-K8 cells to DMSO enhanced glucose-induced and tolbutamide-stimulated insulin secretion without significant effects on basal secretion or potassium responsiveness. Calcium influx was enhanced during glucose and tolbutamide treatments, suggesting that DMSO's mechanism of action is upstream of calcium-dependent insulin granule exocytosis. Based on these studies, investigators should use caution when conducting experiments with DMSO in the MIN6-K8 cell line and should report all DMSO concentrations when used as a solvent.

Keywords: Diabetes; Dimethyl sulfoxide; Drug discovery; Drug screening; Glucose; Insulin secretion.

Fig. 1

DMSO effects on MIN6-K8 cells. Insulin secretion due to DMSO co-treatment with 2.8mM glucose (a),11.2mM glucose (b), 2.8mM glucose + 100μM tolbutamide (c), 2.8mM glucose + 60mM K⁺ (d). Insulin secretion due to 2.5% DMSO co-treatment with various concentrations of glucose (e). Ca²⁺ influx +/− 2.5% DMSO co-stimulated with 16.7mM glucose (f), 2.8mM glucose + 100μM tolbutamide (g), or 2.8mM glucose + 60mM K⁺ (h). DNA in supernatant following 30 minutes of stimulation with 16.7mM glucose +/− 2.5% DMSO (i). Gray triangles: 2.5% DMSO, black circles: Controls (e-h). Statistics: 2-way ANOVA with Sidak’s Multiple Comparison test (a, b, e-h); Mann-Whitney U-test (c, d, i). *p<0.05, **p<0.01, ***p<0.001 .