Regulation of Pancreatic Beta Cell Mass and Function by Proghrelin Derived Peptides

Abstract

Proghrelin produces three proghrelin derived peptides (PGDP) known for their roles in glucose homeostasis: acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). Only the receptor for AG, growth hormone secretagogue receptor 1a (GHS R1a), is known, however there is evidence for additional receptors for AG, UAG and Ob. Our aim was to determine the actions of PGDP on two beta cell lines, MIN6 and INS-1, which we have shown to contain and lack GHS R1a respectively. PGDP increased proliferation in INS-1 but not MIN6 cells, measured by BrdU incorporation. AG decreased apopotosis in both cell lines, measured by decreased levels of activated caspase 3. Insulin secretion was investigated in INS-1 cells, where PGDP modulated insulin release in a glucose dependent manner. Our results indicate that PGDP modulate beta cell mass in the presence and absence of GHS R1a, and present a detailed anaylsis of insulin secretion in INS-1 cells.