Glucose-induced metabolic oscillations parallel those of Ca(2+) and insulin release in clonal insulin-secreting cells. A multiwell approach to oscillatory cell behavior.
Insulin secretion from glucose-stimulated pancreatic beta-cells is oscillatory, and this is thought to result from oscillations in glucose metabolism. One of the primary metabolic stimulus-secretion coupling factors is the ATP/ADP ratio, which can oscillate as a result of oscillations in glycolysis. Using a novel multiwell culture plate system, we examined oscillations in insulin release and the ATP/ADP ratio in the clonal insulin-secreting cell lines HIT T-15 and INS-1. Insulin secretion from HIT cells grown in multiwell plates oscillated with a period of 4 min, similar to that seen previously in perifusion experiments. Oscillations in the ATP/ADP ratio in cells grown under the same conditions also occurred with a period of 4 min, as did oscillations in [Ca(2+)](i) monitored by fluorescence microscopy. In INS-1 cells oscillations in insulin secretion, the ATP/ADP ratio, and [Ca(2+)](i) were also seen, but with a shorter period of about 1.5 min. These observations of oscillations in the ATP/ADP ratio are consistent with their proposed role in driving the oscillations in [Ca(2+)](i) and insulin secretion. Furthermore, these data show that, at least in the clonal beta-cell lines, cell contact or even circulatory connection is not necessary for synchronous oscillations induced by a rise in glucose.
Deeney
J T
JT
The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
Köhler
M
M
Kubik
K
K
Brown
G
G
Schultz
V
V
Tornheim
K
K
Corkey
B E
BE
Berggren
P O
PO
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007328:Insulin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium