Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice.

Objectives: We investigated the influence of leucine supplementation on insulin secretion and on some proteins related to insulin secretion in malnourished mice.

Methods: Swiss mice (aged 21 days) received isocaloric normo-17% (NP) or 6% low-protein (LP) diet for 120 days. Half of the NP and LP mice received 1.5% leucine in the drinking water during the last 30 days (NPL and LPL, respectively).

Results: The LP mice were hypoinsulinemic compared with the NP group, whereas LPL mice exhibited increased insulinemia in the fed state versus LP mice. The LP mouse islets were less responsive to 22.2 mM glucose, 100 microM carbachol (Cch), and 10 mM leucine than the NP group. However, LPL islets were more responsive to all these conditions compared with the LP group. The muscarinic type 3 receptor, (M3R) Cabeta2, and PKC-alpha protein contents were reduced in LP compared with NP islets but significantly higher in LPL than LP islets. The p-AKT/AKT ratio was higher in LPL compared with LP islets.

Conclusions: Leucine supplementation increases insulin secretion in response to glucose and leucine and to agents that potentiate secretion, such as Cch, in malnourished mice. The enhanced levels of M3R, Cabeta2, and PKC-alpha proteins, as well as of the p-AKT/AKT ratio, may play a role in this process.