Figure 1.

Divergent effects of cAMP-increasing agents on glucagon secretion and involvement of PKA.

(A) Glucagon secretion measured from isolated mouse islets in 0 mM glucose (Ctrl) and in the presence of 100 nM GLP-1, 100 nM GIP or 5 μM adrenaline (Adr). ***p<0.001 vs. ctrl;

(B) As in A, but in the presence of 10 μM of the PKA-inhibitor 8-Br-Rp-cAMPS as indicated. ††p<0.01 vs. Ctrl; ‡p<0.05, ‡‡‡p<0.001 for comparison with corresponding values in A. Data have been normalized to control (10.4±0.5 pg/islet/h; n=8-16).

(C) Glucagon secretion measured in the absence (◇) and presence (■) of 100 nM GLP-1 at different glucose concentrations (1-20 mM). **p<0.01 and ***p<0.001 for effect of GLP-1 compared at the respective glucose concentrations. Data have been normalized to control (1 mM glucose; 30.4±1.5 pg/islet/h; n=8).

(D) Glucagon secretion measured at 3 mM glucose in the absence and presence of 100 nM GLP-1 with or without addition of adrenaline (Adr, 5 μM). Data have been normalized to value at 1 mM (in C; 30.4±1.5 pg/islet/h; n=8). *p<0.05, ***p<0.001 vs control and †††p<0.001 vs. GLP-1.

(E) Effects of 10 nM GLP-1 in the absence and presence of 100 nM of the SSTR2 antagonist CYN154806 as indicated. Glucose was presented at 1 mM. Data have been normalized to control (2.1±0.1 pg/islet/h, n=7). **p<0.01 and ***p<0.001 vs control and ††p<0.01 vs. CYN154806 alone.

(F) Expression of GLP-1 (Glp1r), GIP (Gipr) and β1 and β2-adrenergic receptors (Adrb1 and Adrb2) in mouse β-cells.

(G) Same as in F but using mouse α-cells. Data have been normalized to Glp1r expression in mouse β-cells. Note use of different ordinate scales in F-G.

(H) Fraction GLP-1R-positive cells of insulin- (β-cells) and glucagon-positive (α-cells).

(I) Glucagon secretion at 1 mM glucose (Ctrl) and in the presence of 1 μM of exendin-(9-39) (Ex 9-39) and/or 100 nM GLP-1 as indicated. Data have been normalized to control (9.3±0.3 pg/islet/h; n=11-12). ***p<0.001 vs control; †††p<0.001 vs GLP-1 alone.