Notch1 signaling is an important regulator of embryonic development and cell fate decision. Notch1 signaling is also expressed in adult pancreas but there is no study on the role of Notch1 in glucose homeostasis and islet mass in adult pancreas. Here, we investigated the role of Notch1 in glucose homeostasis and islet mass using Notch1 Antisense Transgenic (NAS) mice. We conducted an IPGTT and IPITT in 8-week-old male NAS mice and C57BL/6 mice (control mice). Insulin secretion capacity was measured by GSIS and perifusion. Morphology of pancreatic islet and β cell was conducted in two groups and transcription factors were evaluated. NAS mice showed higher glucose levels and lower insulin secretion in IPGTT. There was no significant difference in insulin resistance. Total islet and β cell masses were decreased in NAS mice. The number of large islets (≥ 250 μm) decreased while that of small islet (< 250 μm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Our study provides that Notch1 inhibition decreased insulin secretion without any alterations in insulin resistance and decreased islet and β cell mass in the adult pancreas in NAS model. It is thought that Notch1 inhibition early suppresses islet proliferation and induces differentiation of not fully proliferated small islets.
In conclusion, the Notch signaling pathway may play an important role in beta cell mass and development of diabetes.
Y. Eom: None. K. Kim: None. B. Kim: None.
Korea Health Technology R&D Project (A101711, HI14C2539); Korean Ministry of Health, Welfare, and Family Affairs
