Date of Award


Degree Type


Degree Name

Master of Science




Dr. Rennian Wang

Second Advisor

Dr. Subrata Chakrabarti

Third Advisor

Dr. Martin Sandig


Integrin-extracellular matrix (ECM) interactions are important determinants of beta cell behaviours. The pi integrin is a well known regulator of beta cell activities, however, little is known of its associated a subunits. In the present study, api integrin expression was examined in rat insulinoma cell line, INS-1 cells, to identify their role in beta cell survival and function. Seven a subunits were identified, of which a3pi was most highly expressed. Remarkable increases in adhesion, proliferation and insulin secretion were observed in cells cultured on collagen I or IV. To investigate relationships between a3pi integrin and these matrices, cells were treated with immunoneutralizing antibodies for pi or a3 integrin and cultured on collagen I or IV. Anti-pi treatments caused marked decreases in adhesion and proliferation on both collagens, while perturbed a3 function led to changes only on collagen IV. Cellular insulin contents and secretion were greatly impaired on collagen I and IV upon anti-pi treatment, while a3 integrin blockade caused similar changes only on collagen IV. Furthermore, perturbing either pi or a3 integrin function decreased FAK and ERK1/2 phosphorylation and increased caspase3 cleavage. Blocking a3 integrin function reduced Akt and GSK3-P phosphorylation and decreased XIAP expression; however, these changes were not observed upon anti-pi treatments. These results suggest that dynamic integrin-ECM interactions are critical for modulating beta cell survival and function through highly specialized signaling cascades.



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