Current and ongoing beta cell research is presented in this weekly seminar by faculty, postdoctoral fellows and students. If you are interested in attending the Beta Cell Interest Group (BIG) seminars and joining the BIG community, please contact David Jacobson.

Keywords: Beta cell Islet

Record History
Added on September 7, 2016 at 4:50 PM by Brown, Deborah
Modified on December 29, 2016 at 3:02 PM by Brown, Deborah
Shared with (contributions)
BIG: Beta Cell Interest Group (BIG) Master

Meeting Details

Start Date / Time January 4, 2017 at 9:00 AM
End Date / Time January 4, 2017 at 9:55 AM
Duration 55 minutes
Location 512 Light Hall
Presenter Name Matthew Dickerson, PhD (Jacobson lab)
Presentation Title “Exploring mechanisms that regulate the TALK-1 K+ channel and its role in the function of β-cells under inflammatory conditions”
Status This meeting has already occurred

Meeting Agenda/Notes

The type 2 diabetes (T2D)-associated K+ channel, TALK-1, is the most highly expressed K+ channel found in the islet. We have demonstrated that TALK-1 channels limit β-cell glucose-stimulated Ca2+ influx and insulin secretion (GSIS). However, the mechanisms governing TALK-1 channel function as well as its role during the onset of T2D are largely unknown. Here, we investigate the interaction of TALK-1 with osteopontin (OPN), a protein upregulated under pre-diabetic conditions, as well as the role of TALK-1 in β-cells exposed to inflammatory cytokines, which are also commonly upregulated under pre-diabetic conditions. We discovered that OPN activates TALK-1 channel activity, which may serve to moderate abnormally high insulin secretion during the onset of T2D in order to preserve β-cell health. We also determined that exposure to inflammatory cytokines significantly downregulates islet TALK-1 transcript and protein accompanied by a reduction in β-cell TALK-1 channel currents and membrane potential depolarization. Following cytokine exposure basal intracellular Ca2+  increased and 1st phase glucose-stimulated Ca2+ influx decreased independent of TALK-1 while 2nd phase glucose-stimulated Ca2+ influx decreased only in TALK-1 knockout islets. Similarly, GSIS only decreased in TALK-1 knockout islets.  Additionally, cytokine exposure increased endoplasmic reticulum (ER) Ca2+ stores in WT but not TALK-1 KO islets. These findings suggest that TALK-1 may serve a protective role in the ER of β-cells by facilitating increased storage of ER Ca2+ in response to inflammation, which assists in the maintenance of GSIS.