Premium
Probing the intra‐islet control of beta cell function (1108.3)
Author(s) -
Elrick Mollisa,
Yosten Gina,
Salvatori Alison,
Samson W.K.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1108.3
Subject(s) - proglucagon , endocrinology , medicine , hyperglucagonemia , alpha cell , islet , glucagon , biology , somatostatin , beta cell , alpha (finance) , receptor , glucagon like peptide 1 , population , insulin , diabetes mellitus , type 2 diabetes , construct validity , nursing , environmental health , patient satisfaction
Neuronostatin (NST) is produced in pancreatic delta cells from the somatostatin preprohormone, and has been shown to inhibit glucose‐stimulated insulin secretion from beta cells of primary islets, but not from isolated beta cell cultures. We have demonstrated that NST stimulates glucagon release and have hypothesized that this is necessary for the peptide’s in vivo effect to impair glucose tolerance. Here we demonstrate the action of NST to increase proglucagon message in alpha cells and identify a potential mechanism to be via phosphorylation of protein kinase A. The NST receptor, GPR107, is abundantly expressed in the pancreas, in particular in the alpha cell population and both the effect on proglucagon mRNA levels and PKA phosphrylation are absent in alpha cells in which the expression of the NST receptor has been compromised using siRNA. Taken together with our observation that NST infusion in conscious rats impairs glucose tolerance and that plasma levels of the peptide are elevated in the fasted compared to the fed or fasted‐refed state, our studies support the hypothesis that endogenous NST is a physiologically relevant determinant of islet cell function and may contribute to the hyperglucagonemia of the prediabetic state. Grant Funding Source : NIH HL66023