Gaegurin-6 stimulates insulin secretion through calcium influx in pancreatic beta Rin5mf cells.
Gaegurin-6, an antimicrobial peptide that belongs to the alpha-helix family, was isolated from the skin of Rana rugosa. Gaegurin-6 contains a hydrophobic motif at the N-terminus and a helical region at the C-terminus. Although gaegurin-6 has been implicated in cell signaling, the precise role in insulin secretion is currently unknown. We have attempted to determine whether gaegurin-6 affects insulin secretion and tried to elucidate the relationship between the structural motifs and biological activity. In this study, we have shown that gaegurin-6 stimulates insulin secretion and also increases the intracellular calcium concentration in pancreatic beta Rin5mf cells. Moreover, a corollary study revealed that both the hydrophobicity of the N-terminus and the disulfide bridge of the C-terminus of gaegurin-6 are critical for its effects on insulin secretion. Membrane pore-forming ability is also observed in gaegurin-6, but not in the linear form or the N-terminus hydrophobic amino acid-deleted form. We further showed that these regions of gaegurin-6 are responsible for calcium influx in pancreatic beta Rin5mf cells. Taken together, these results indicate that gaegurin-6 can affect insulin secretion in pancreatic beta cells through the modulation of calcium influx.
Kim
Ji Hae
JH
Department of Anatomy, Korea University College of Medicine, 126-1, 5 ga, Anam-dong, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
Lee
Jung Ok
JO
Jung
Jin Hee
JH
Lee
Soo Kyung
SK
You
Ga Young
GY
Park
Sun Hwa
SH
Kim
Hyeon Soo
HS
D020816:Amino Acid Motifs; D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats
D029845:Amphibian Proteins; D007328:Insulin; D011498:Protein Precursors; C119329:gaegurin 6; D002118:Calcium