Endocrine Abstracts

Background: There are now several lines of evidence indicating that a decrease in beta-cell mass, resulting from an increase in apoptosis, is a key feature in both type-1 (T1DM) and -2 diabetes (T2DM). Interestingly, recent studies suggest that the insulin receptor signalling cascade may play key functions in preventing beta-cells from undergoing apoptosis. However, the molecular basis underlying these events remains to be determined.

Aims: this study examined the possible protective effects of glucose and exogenous insulin on basal and cis-platinum-induced apoptosis in MIN6 cells.

Methods: MIN6 cells were incubated in 2.5, 5.5, 10, 17 or 25mM glucose-containing media either in the presence or absence of 100 microM cis-platinum for 16-168 hours, and the extent of apoptosis was determined by measuring DNA fragmentation and caspase-3 activity.

Results: Exogenous administration of insulin (1nM to 10 microM) reduced the cis-platinum-induced apoptosis in a concentration-dependent manner, but failed to completely rescue the cells from death (% inhibition of caspase 3 activity: 1nM insulin: 0.1%; 10nM insulin: 28.2%; 100nM insulin: 33.6%; and 10 microM insulin: 37.4%). Increasing the glucose concentration from 2.5 to 25 mM also reduced apoptosis in a concentration-dependent manner (% inhibition of caspase 3 activity determined at 2.5 mM glucose: 5.5mM glucose: 10.3±4.7%; 10mM glucose: 19.8±3.4%; 17mM glucose: 26.1±4.1%; 25mM glucose: 31.7±4.5%; mean±SEM, n=4; p<0.05 by ANOVA). Treatment of MIN6 cells with an anti-insulin serum in the presence of 25mM glucose induced a 2.5-fold increase in caspase-3 activity and this effect was completely abolished when an excess of insulin was added in the medium.

Conclusion: These results suggest that glucose-stimulated insulin secretion mediates the glucose protective effect against apoptosis in MIN6 cells, and that the insulin signalling pathway may be a key determinant in the processes involved in the regulation of the beta-cell mass plasticity.