Discipline: Biological Sciences
Subcategory: Physiology and Health
Mallory Brayer - University of Scranton
Co-Author(s): Ben Thompson, University of Michigan, Ann Arbor, MI; Les Satin, University of Michigan, Ann Arbor, MI
Type 1 diabetes (T1D) is an autoimmune disease where pancreatic beta cell dysfunction and death reduces beta cell mass and insulin secretion, causing elevated fasting blood sugar. Cytokines mediate beta cell dysfunction in T1D and upregulate the expression of inducible nitric oxide synthase (iNOS) which synthesizes nitric oxide (NO) from L-arginine. To test how overnight cytokine treatment affects islet function, isolated mouse islets were cultured with a cytokine cocktail with or without the iNOS inhibitor L-NMMA. The islet free calcium (Ca2+) sensing dye fura-2 was used to monitor islet Ca2+ oscillations in response to 5 – 20 mM glucose. Cytokine treatment abolished islet Ca2+ oscillations. However, inclusion of L-NMMA prevented cytokine action. This suggests that cytokine-induced beta cell dysfunction requires the iNOS activation. While we do not know the molecular target(s) of cytokine-induced NO, ATP production by metabolism is a likely contributor.
Funder Acknowledgement(s): This research was funded by the National Science Foundation through the University of Michigan School of Pharmacy Interdisciplinary REU Program and research grants to the Satin Lab from JDRF and NIDDK/NIH.
Faculty Advisor: Leslie Satin, firstname.lastname@example.org
Role: I helped in experimental design. I ran all experiments and collected all data for this project. I also did all the data analysis and writing. I also did the majority of the poster design.