Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice. Reply to: de Souza JC, de Oliveira CAM, Carneiro EM et al. [letter]

Excerpt

To the Editor: In their letter [1], de Souza and colleagues point out important differences between our study [2] and their subsequent report on the role of the LDL receptor (LDLr) in islet cholesterol handling. In contrast to their data [3], we did not detect a significant difference between islet cholesterol levels in mice lacking LDLr (Ldlr ^–/–) and control mice [2]. Accordingly, we found no difference in glucose tolerance or insulin secretion in Abca1 ^fl/fl;Ldlr ^+/+ mice compared with Abca1 ^fl/fl;Ldlr^–/– mice on a chow diet. This is in agreement with previous literature showing no effect of LDLr deficiency on fasting glucose levels and glucose tolerance in chow-fed mice and slightly improved glucose tolerance in mice fed a Western-type diet [4, 5]. At this point the reasons for the discordant results obtained by Bonfleur and colleagues are not clear, as both groups used mice bred on a pure C57Bl6 background at similar ages (16 weeks). However, the results of both groups point to the ability of circulating and cellular cholesterol to significantly influence islet function. …