title: Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced potentiation of leucine/glutamine-stimulated insulin secretion.
abstract: Genistein has been reported to potentiate glucose-stimulated insulin secretion (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A (PKA) was shown to play a role in the genistein-induced potentiation effect on GSIS. The aim of the present study was to elucidate the mechanism of genistein-induced potentiation of insulin secretion. Genistein augmented insulin secretion in INS-1 cells stimulated by various energy-generating nutrients such as glucose, pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by depolarizing agents such as KCl and tolbutamide, or Ca(2+) channel opener Bay K8644. Genistein at a concentration of 50 μM showed a maximum potentiation effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to inhibit the activity of tyrosine kinase. Inhibitor studies as well as immunoblotting analysis demonstrated that activation of PKA was little involved in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the other hand, all the inhibitors of Ca(2+)/calmodulin kinase II tested, significantly diminished genistein-induced potentiation. Genistein also elevated the levels of [Ca(2+)]i and phospho-CaMK II. Furthermore, genistein augmented Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These data suggest that the activation of CaMK II played a role in genistein-induced potentiation of insulin secretion.
authors.affiliation: Institute for Medical Science, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hyo-Eun
authors.initials: HE
authors.lastname: Kim
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Ha-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Kwag
authors.forename: Byung-Kyu
authors.initials: BK
authors.lastname: Lee
authors.forename: Ki-Woong
authors.initials: KW
authors.lastname: Cho
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004357:Drug Synergism; D019833:Genistein / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
chemical_list: D007328:Insulin; D005973:Glutamine; D019833:Genistein; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D007930:Leucine; D002118:Calcium