Characterization of preptin-induced insulin secretion in pancreatic β-cells

    1. Akio Inui
    1. Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
      1Department of Bioorganic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1180, Japan
      2Department of Medical Research, Chi‐Mei Medical Center, Tainan 710-04, Taiwan
    1. (Correspondence should be addressed to A Inui; Email: inui{at}


    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 Ca2+ [Ca2+]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.

    • Received in final form 6 July 2012
    • Accepted 11 July 2012
    • Made available online as an Accepted Preprint 11 July 2012
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