Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor(s)

Rennian Wang

Abstract

Integrin β1 is essential for pancreatic beta-cell development and maintenance throughout life in rodents and human fetal islets. However, the effects of a postnatal β1 integrin knockout (β1KO) specific to pancreatic beta-cells of mice is undetermined. We generated mice with CreERT recombinase specific to the mouse insulin promoter (MIP), allowing us to induce a β1KO upon injection of tamoxifen (MIPβ1KO model).

At 3-4 weeks of age tamoxifen was injected and mice were sacrificed at 8 (male) and 16 weeks (female) post-tamoxifen. MIPβ1KO mice had impaired glucose tolerance, reduced beta-cell mass and islet density. The impairment in glucose tolerance remained in aged mice. Male MIPβ1KO mice also had impaired insulin expression and secretion, along with reduced Pdx-1, p-FAK, p-ERK, and p-Akt protein levels. Insulin exocytosis proteins were also reduced in male MIPβ1KO mice. These findings demonstrate a significant role for β1 integrin in the survival and function of adult murine beta-cells.

Available for download on Tuesday, May 01, 2018


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