The Insulin Level was Significantly Decreased in Transgenic Mice Co-overexpressing the Human Insulin Degrading Enzyme and Insulin-siRNA

To determine whether a transgene-based small interfering RNA (siRNA) for insulin and an overexpression of human insulin degrading enzyme (hIDE) decrease the insulin level in transgenic mice, pH1/siRNA insulin -pCMV/hlDE fusion gene for insulin inhibition were overexpressed in the transgenic (Tg) mice via microinjection. By screening 34 newborn founder mice, three transgenic mice were identified by polymerase chain reaction (PCR) and southern blot analysis using specific DNA. In each tissue of these transgenic mice, high expression of hIDE transcripts was detected both in the liver and muscle. Also, these mice were showed the high level of glucose by glucose tolerance test and high activity of hIDE in liver protein. These results suggest that these transgenic mice for the suppression of insulin secretion by the specific siRNAs and the insulin degradation by an overexpression of hIDE protein may be useful on the study of diabetes-related disease.