Inhibition of phosphatases and increased Ca2+ channel activity by inositol hexakisphosphate.
Inositol hexakisphosphate (InsP6), the dominant inositol phosphate in insulin-secreting pancreatic beta cells, inhibited the serine-threonine protein phosphatases type 1, type 2A, and type 3 in a concentration-dependent manner. The activity of voltage-gated L-type calcium channels is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obtained in the presence of InsP6 might result from the inhibition of phosphatase activity. Glucose elicited a transient increase in InsP6 concentration, which indicates that this inositol polyphosphate may modulate calcium influx over the plasma membrane and serve as a signal in the pancreatic beta cell stimulus-secretion coupling.
Larsson
O
O
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
Barker
C J
CJ
Sjöholm
A
A
Carlqvist
H
H
Michell
R H
RH
Bertorello
A
A
Nilsson
T
T
Honkanen
R E
RE
Mayr
G W
GW
Zwiller
J
J
Berggren
P O
PO
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D015640:Ion Channel Gating; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010833:Phytic Acid / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D007295:Inositol Phosphates; D007294:Inositol; D010833:Phytic Acid; D010749:Phosphoprotein Phosphatases; D005947:Glucose; D002118:Calcium