Comparison of glucose tolerance between wild-type mice and mice with double knockout of neuromedin U and neuromedin S.

Recently, it has been proposed that neuromedin U (NMU) is "decretin", which suppresses insulin secretion from the pancreas in vitro. Here we examined the possible involvement of NMU in insulin secretion in vivo by comparing the plasma glucose and insulin levels of wild-type mice with those of double knockout (D-KO) of the NMU and neuromedin S (NMS) genes, as NMS binds to the neuromedin U receptor. If NMU is, in fact, "decretin", which inhibits insulin secretion from the pancreas, then NMU-deficient mice might result in higher plasma insulin levels than is the case in wild-type mice, or injection of NMU lead to suppression of plasma insulin level. In this study, we found that the fasting plasma level of insulin was not increased in D-KO mice. Glucose tolerance tests revealed no significant difference in plasma insulin levels between wild-type mice and D-KO mice under non-fasting conditions. After peripheral injection of NMU, plasma glucose and insulin levels did not show any significant changes in either wild-type or D-KO mice. Glucose tolerance testing after 3 weeks of high fat feeding revealed no significant difference in plasma insulin levels during 60 min after glucose injection between wild-type and D-KO mice. These results suggest that even if NMU is a decretin candidate, its physiological involvement in suppression of insulin secretion may be very minor in vivo.