1748-P: Assessing the Presence of Delta-Cell–Mediated Electrical Coupling in the Islet

Abstract

Somatostatin-producing delta cells play an important role in the regulation of paracrine cross talk in the islet through inhibition of insulin and glucagon secretion by beta and alpha cells, respectively. However, recent studies have suggested the presence of electrical coupling via gap junctions between delta and beta cells. Electrical coupling mediated cross-talk would support the correlation between pulsatile insulin and somatostatin release and reveal a structural source of cell-cell communication within the islet. To test whether beta and delta cells are gap junction coupled, we measured the permeability of cell to cell connections and the relative dynamics of Ca2+. Islets of Sst-Cre;Rosa-LSL-tdTomato mice were used which show delta-cell specific labelling. They were then loaded with the cationic dye rhodamine-123 at 5mM glucose to measure performance of fluorescence recovery after photobleaching to assess gap junction coupling of delta cells and non-delta cells. Calcium dynamics were assessed using calcium dye Fluo-4 upon stimulating the islet from low glucose (2mM or 5 mM) to high glucose(11mM). No significant differences between recovery rate were observed when comparing delta cells and beta cells (p>0.05), which indicates some level of gap junction permeability among delta cells exists. The calcium activity of a population of delta cells was similar to those of neighboring beta cells, indicating a functional connection exists between these cell types. Furthermore, first-responder beta cells showed a preferential proximity to delta cells suggesting an impact of delta cells on functional sub-populations of nearby beta-cells. These results suggest a possible feedback system exists in the islet that is governed by electrical coupling of delta cells, which is important for both the function of beta cells and insulin secretion, and may also impact secretion of other islet hormones. Disclosure C.H.Levitt: None. R.K.Benninger: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK116073, R01DK102950, R01DK106412)