Characterization of preptin-induced insulin secretion in pancreatic β-cells.
We aimed to characterize the effects of preptin on insulin secretion at the single-cell level, as well as the mechanisms underlying these changes, with respect to regulation by intracellular Ca(2+) [Ca(2+)](i) mobilization. This study assessed the effect of preptin on insulin secretion and investigated the link between preptin and the phospholipase C (PLC)/protein kinase C (PKC) pathway at the cellular level using fura-2 pentakis(acetoxymethyl) ester-loaded insulin-producing cells (Min 6 cells). Our results demonstrate that preptin promotes insulin secretion in a concentration-dependent manner. Using a PLC inhibitor (chelerythrine) or a PKC inhibitor (U73122) resulted in a concentration-dependent decrease in insulin secretion. Also, preptin mixed with IGF2 receptor (IGF2R) antibodies suppressed insulin secretion in a dose-dependent manner, which indicates that activation of IGF2R is mediated probably because preptin is a type of proIGF2. In addition, preptin stimulated insulin secretion to a similar level as did glibenclamide. The activation of PKC/PLC by preptin stimulation is highly relevant to the potential mechanisms for increase in insulin secretion. Our results provide new insight into the insulin secretion of preptin, a secreted proIGF2-derived peptide that can induce greater efficacy of signal transduction resulting from PLC and PKC activation through the IGF2R.
Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kai-Chun
KC
Cheng
Ying-Xiao
YX
Li
Akihiro
A
Asakawa
Miharu
M
Ushikai
Ikuo
I
Kato
Yuki
Y
Sato
Juei-Tang
JT
Cheng
Akio
A
Inui
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D055571:Secretory Pathway / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; C443100:preptin; D007335:Insulin-Like Growth Factor II; D005947:Glucose; D005905:Glyburide