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Oscillatory Signaling and Insulin Release in Human Pancreatic ß-Cells Exposed to Strontium¹

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Address all correspondence and requests for reprints to: Prof. Bo Hellman, Department of Medical Cell Biology, Biomedicum, Box 571, S-751 23 Uppsala, Sweden.

Oscillatory signaling and insulin release were studied in isolated pancreatic islets and ß-cells obtained from human cadaveric organ donors. Taking advantage of Sr²⁺ as an analog for Ca²⁺, it was possible to demonstrate glucose-induced rhythmic activity in individual ß-cells identified by immunostaining. Glucose-induced slow oscillations of Sr²⁺ (frequency, 0.1–1.0/min) were sometimes seen at a sugar concentration as low as 3 mM. Addition of 20 nM glucagon resulted in a broadening of the oscillations or in their transformation into sustained elevation. Moreover, the presence of glucagon resulted in the appearance of short transients of Sr²⁺, which disappeared after exposure to the intracellular Ca²⁺-adenosine triphosphatase inhibitor thapsigargin. Digital image analyses indicated that slow oscillations can be synchronized among cells in small aggregates and intact islets. The rhythmic activity in the glucose-stimulated ß-cell had its counterpart in pulsatile insulin release when single islets were perifused with a Sr²⁺-containing medium. It is concluded that the human ß-cell has oscillatory signaling for insulin release similar to that observed in experimental animals.

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