Electronic Thesis and Dissertation Repository


Master of Science




Rennian Wang


The expression of insulin receptor (IR) in β-cells suggests an autocrine role for insulin signalling in β-cell function and regulation. Studies have demonstrated that β-cell Ir knockout (βIrKO) mice develop age-dependent glucose intolerance. We investigated the temporal role of β-cell IR signaling in pre- and postnatal islet development and function, and under high-fat diet stress, using a tamoxifen-inducible Cre-recombinase Ir knockout mouse model.

Prenatal βIrKO mice exhibited increased mean islet area, β-cell area, and islet area percentage. Additionally, there was upregulation of insulin-like growth factor-2 levels, increased Akt activity, and increased proliferation in islets. Postnatally-induced βIrKO mice did not exhibit impaired glucose tolerance at 4, 8, and 20 weeks post-tamoxifen. Similarly, no differences were observed between groups on high-fat diet. Results suggest that while loss of fetal β-cell IR causes an islet growth response through alternate pathways, postnatal β-cell IR may not play a pivotal role for adult β-cell function.