Research Project
Grant-in-Aid for Young Scientists (B)
In this study, we investigated the synergistic role of human IAPP (hIAPP) and autophagy dysfunction in the pathogenesis of diabetes. In the previous study we reported that reduced autophagic acitivity in beta cells caused impaired glucose tolerance. Physiological expression of human IAPP using hIAPP knockin strategy further exacerbated glucose intolerance of mice with beta-cell specific autophagy deficiency. Induction of hIAPP in insulinoma cells and in hIAPP knockin mice resulted in inhibition of beta cell proliferation associated with decreased phosphorylation of insulin receptor. These results suggested that inhibition of insulin signaling by hIAPP may be involved in the loss of compensatory proliferation of beta cells and impaired glucose tolerance.
