Long Term Effects of Aminoguanidine on Insulin Release and Biosynthesis: Evidence That the Formation of Advanced Glycosylation End Products Inhibits B Cell Function1

Chronic hyperglycemia has adverse effects on B cell function. We investigated the possible role of advanced glycosylation end products (AGEs) in glucotoxicity. Rat islets were cultured at different glucose concentrations for 1–6 weeks in RPMI 1640. Culture was performed with or without aminoguanidine (AG), which is known to prevent AGE formation in other tissues. AGE-associated fluorescence (370 nm excitation and 440 nm emission) progressively increased during 6 weeks of culture at 38 mm, but not at 11 or 5.5 mm, glucose. The increase in fluorescence was significantly inhibited by AG. The effects of AG on insulin secretion were tested directly after the culture period as well as after a wash-out period of continued culture at 11 mm glucose in the absence of AG. The presence of AG during culture for 1 week at 38 mm glucose failed to affect basal release at 3.3 mm glucose or stimulated release at 27 mm glucose. AG was ineffective whether tested directly after the culture period or after wash-out. When the s...