Question: 

Impairment of beta-cell function and viability by oxidative stress plays an important role during development of diabetes mellitus. Antioxidant defence mechanisms are extremely low in beta-cells. We tested tempol, a mimetic of superoxide dismutase (SOD), for its ability to protect mouse beta-cells against H₂O₂-induced oxidative stress.

Methods: 

Insulin secretion was measured by radioimmunoassay and electrical activity by MEA technique. Apoptosis was determined by TUNEL staining.

Results: 

Tempol augmented glucose-induced (10mM; G10) electrical activity measured as the fraction of plateau-phase (FOPP) from mouse islets of Langerhans. The FOPP reversibly increased from 44±2% (n=31) to 61±2% (n=11, p2O₂ (300mM) decreased the FOPP in G10 to three-quarter of the control value (n=14; p2O₂-induced change in the FOPP after preincubation with tempol for 30 min (n=7). These data were mirrored by tempol- and H₂O₂-induced changes in glucose-stimulated insulin secretion (GSIS). The GSIS was 2.48± 0.44ng/(h*islet) in G15 and 3.91±0.66 ng/(h*islet) with tempol (n=6). H₂O₂ (100mM) decreased GSIS in G15 to 0.94±0.25 ng/(h*islet) (n=6; p2O₂-induced (25mM, 1h) cell death was diminished by approximately 80% by incubation with tempol (n=3).

Conclusion: 

Increasing the SOD activity protects islet cells against loss of function and mass by an oxidative insult. Thus, enhancement of antioxidant defence mechanisms may prevent or decelerate the development of type-2 diabetes.