Oscillatory signaling and insulin release in human pancreatic beta-cells exposed to strontium.
Oscillatory signaling and insulin release were studied in isolated pancreatic islets and beta-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 beta-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 beta-cell had its counterpart in pulsatile insulin release when single islets were perifused with a Sr2+-containing medium. It is concluded that the human beta-cell has oscillatory signaling for insulin release similar to that observed in experimental animals.
Hellman
B
B
Department of Medical Cell Biology, Uppsala University, Sweden.
Gylfe
E
E
Bergsten
P
P
Grapengiesser
E
E
Berts
A
A
Liu
Y J
YJ
Tengholm
A
A
Westerlund
J
J
D000328:Adult; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D013324:Strontium / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D019284:Thapsigargin; D005934:Glucagon; D014044:Tolbutamide; D000252:Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium; D013324:Strontium