Aberrant function and long-term survival of mouse beta cells exposed in vitro to high glucose concentrations

In vitro culture of murine Langerhans islets usually ends in islet death after 1-3 wk. Given contradictory published data, we studied the influence of glucose on the function and survival of islets from DBA/2 mice. Islets were cultured on plastic microwells, using 1, 2, or 11 g/l glucose concentrations. Using our routine technique, insulin secretion was evaluated after islet incubation for 15 min in basal medium [(sIS), 1 g/l glucose], followed by 15 min in stimulating medium [(sIS), 3 g/l glucose, 20 mM/l arginine, 5 mM/l theoophylline]. Insulin secretion of islets cultured in 1 g/l glucose remained stable and normal over a period of 2 mo [Day 7: bIS, 6.3 +/- 3.1 microU/50 microliters; sIS, 16.6 +/- 6.8 microU/50 microliters. Day 60: bIS, 6.0 +/- 4.0 microU/50 microliters; sIS, 21.3 +/- 10.5 microU/50 microliters]. Islet morphology also remained normal. Islets cultured in 2 g/l glucose showed elevated insulin response under basal and stimulating conditions during 2-3 wk, followed by a dramatic drop in insulin secretion [Day 7: bIS, 19.5 +/- 5.7 microU/50 microliters; sIS, 80.9 +/- 10.7 microU/50 microliters. Day 60: bIS, 5.4 +/- 5.0 microU/50 microliters; sIS, 2.7 +/- 1.4 microU/50 microliters]. Severe morphologic alterations appeared rapidly and islet destruction was nearly complete by 60 days. At 11 g/l glucose, functional and morphological islet alterations were accelerated [Day 7: bIS, 10.3 +/- 2.7 microU/50 microliters; sIS, 18.8 +/- 4.9 microU/50 microliters. Day 21: bIS and sIS almost undetectable].(ABSTRACT TRUNCATED AT 250 WORDS)