Fig. 1.

Strategy for inducing GLP-1 production in pancreatic α cells. (A) Adult pancreatic α cells liberate glucagon from the precursor proglucagon by means of PC2 activity. We hypothesized that adenoviral delivery of PC1/3 (AdPC1/3) to pancreatic α cells would liberate bioactive GLP-1 from the major proglucagon fragment (MPGF). GRPP, glicentin-related pancreatic polypeptide; IP-1 and IP-2, intervening peptides. (B and C) Western blot analysis of PC1/3 expression in control gut (STC-1) cells, InR1-G9 cells (B), and αTC-1 cells (C) 72 h after treatment with AdPC1/3 at moi = 0, 10, or 100. Blots are representative of three or more experiments. (D) Northern blot analysis of proglucagon (PG) mRNA levels in InR1-G9 cells transduced with AdPC1/3 (PC1/3) or Ad5lacZ (lacZ) (representative of three or more experiments). Data are normalized for β-actin and expressed relative to mock-transduced control (Ctl). ∗, P < 0.05 versus control using one-way ANOVA. (E–H) GLP-1 and glucagon (GLGN) secretion by InR1-G9 (E and G) and αTC-1 (F and H) cells after treatment with AdPC1/3 or Ad5lacZ at moi = 0, 10, or 100. ∗, P < 0.05; ∗ ∗, P < 0.01; ∗ ∗ ∗, P < 0.001 compared with Ad5lacZ; n ≥ 3.