Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic beta cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP(7) or IP(7)). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP(7) were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in b cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP(7) in the pancreatic b cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.

Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic beta cells

FIUME, ROBERTA;
2007

Abstract

Inositol pyrophosphates are recognized components of cellular processes that regulate vesicle trafficking, telomere length, and apoptosis. We observed that pancreatic beta cells maintain high basal concentrations of the pyrophosphate diphosphoinositol pentakisphosphate (InsP(7) or IP(7)). Inositol hexakisphosphate kinases (IP6Ks) that can generate IP(7) were overexpressed. This overexpression stimulated exocytosis of insulin-containing granules from the readily releasable pool. Exogenously applied IP7 dose-dependently enhanced exocytosis at physiological concentrations. We determined that IP6K1 and IP6K2 were present in b cells. RNA silencing of IP6K1, but not IP6K2, inhibited exocytosis, which suggests that IP6K1 is the critical endogenous kinase. Maintenance of high concentrations of IP(7) in the pancreatic b cell may enhance the immediate exocytotic capacity and consequently allow rapid adjustment of insulin secretion in response to increased demand.
Illies C.; Gromada J.; Fiume R.; Leibiger B.; Yu J.; Juhl K.; Yang SN.; Barma DK.; Falck JR.; Saiardi A.; Barker CJ.; Berggren PO
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/92950
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