Effect of protein kinase C on glucose-mediated insulin secretion in HIT-T15 cells.
OBJECTIVE
To clarify the regulation of protein kinase C on glucose-mediated insulin secretion.


METHODS
We examined the effect of protein kinase C on the cytosolic free Ca(2+) concentration ([Ca(2+)]i) and the activity of Ca(2+)-activated K(+) channels (K(Ca)-channel) in the insulinoma cell line, HIT-T15.


RESULTS
Glucose at a concentration of 10 mmol/L increased the secretion of insulin. This increase was partly inhibited by 1 nmol/L staurosporine, a protein kinase C inhibitor. Staurosporine (1 nmol/L) also attenuated the glucose-induced elevations in [Ca(2+)]i. On the contrary, glibenclamide (100 nmol/L) specifically blocked ATP-sensitive K(+) channels, and increased both [Ca(2+)]i and insulin secretion, but staurosporine had no effect on them. Patch clamp studies showed that 10 mmol/L glucose almost completely blocked K(Ca) channel activity, an effect that was reversed by 1 nmol/L staurosporine. Phorbol 12-myristate 13-acetate (1 mmol/L), a protein kinase C activator, also decreased K(Ca) channel activity.


CONCLUSIONS
These results indicate that the activation of protein kinase C is involved in the glucose-induced release of insulin by modulating K(+) channel function in HIT-T15 cells.
Akiyoshi
H
H
Department of Nutrition, School of Medicine, The University of Tokushima. Tokushima City, Japan.
Nakaya
Y
Y
D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007328:Insulin; D011493:Protein Kinase C; D005947:Glucose