, a bio/informatics shared resource is still "open for business" - Visit the CDS website
|Start Date / Time||January 4, 2017 at 9:00 AM|
|End Date / Time||January 4, 2017 at 9:55 AM|
|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|
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.