OSCILLATORY SIGNALING AND INSULIN RELEASE IN HUNAN PANCREATIC BETA-CELLS EXPOSED TO STRONTIUM

Oscillatory signaling and insulin release were studied in isolated pan creatic islets and beta-cells obtained from human cadaveric organ dono rs. Taking advantage of Sr2+ as an analog for Ca2+, it was possible to demonstrate glucose-induced rhythmic activity in individual beta-cell s identified by immunostaining. Glucose-induced slow oscillations of S r2+ (frequency, 0.1-1.0/min) were sometimes seen at a sugar concentrat ion as low as 3 mM. Addition of 20 nM glucagon resulted in a broadenin g of the oscillations or in their transformation into sustained elevat ion. Moreover, the presence of glucagon resulted in the appearance of short transients of Sr2+, which disappeared after exposure to the intr acellular Ca2+-adenosine triphosphatase inhibitor thapsigargin. Digita l image analyses indicated that slow oscillations can be synchronized among cells in small aggregates and intact islets. The rhythmic activi ty in the glucose-stimulated beta-cell had its counterpart in pulsatil e insulin release when single islets were perifused with a Sr2+-contai ning medium. It is concluded that the human beta-cell has oscillatory signaling for insulin release similar to that observed in experimental animals.