Inositol hexakisphosphate stimulates non-Ca2+-mediated and primes Ca2+-mediated exocytosis of insulin by activation of protein kinase C.
D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), formed via complex pathways of inositol phosphate metabolism, composes the main bulk of inositol polyphosphates in the cell. Relatively little is known regarding possible biological functions for InsP6. We now show that InsP6 can modulate insulin exocytosis in permeabilized insulin-secreting cells. Concentrations of InsP6 above 20 microM stimulated insulin secretion at basal Ca2+-concentration (30 nM) and primed Ca2+-induced exocytosis (10 microM), both effects being due to activation of protein kinase C. Our results suggest that InsP6 can play an important modulatory role in the regulation of processes such as exocytosis in insulin-secreting cells. The specific role for InsP6 can then be to recruit secretory granules to the site of exocytosis.
Efanov
A M
AM
The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, S-17176 Stockholm, Sweden.
Zaitsev
S V
SV
Berggren
P O
PO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects*; D008566:Membranes / Q000502:physiology; D008954:Models, Biological; D010833:Phytic Acid / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007328:Insulin; D010833:Phytic Acid; D011493:Protein Kinase C; D002118:Calcium