Fig. 7: Lack of α-cell G_s signaling leads to impaired glucagon release under different experimental conditions in vivo.

a, b Glucagon release following insulin-induced hypoglycemia. α-GsKO mice and control littermates were injected with insulin (1 U/kg, i.p.), and plasma glucagon (a) and blood glucose (b) levels were measured at the indicated time points (n = 8 per group). c, d Glucagon secretion after 2-DG-induced glucopenia. α-GsKO and control mice were injected with 2-DG (500 mg/kg, i.p.), and plasma glucagon (c) and blood glucose (d) levels were measured at the indicated time points (control, n = 5; α-GsKO, n = 7). e–g Treatment of mice with a mixture of GIP and alanine. α-GsKO and control mice were injected i.p. with a combination of GIP (4 nmol/kg) and alanine (0.325 g/kg), and plasma glucagon (e), plasma insulin (f), and blood glucose (g) levels were measured 15 min later (n = 8 per group). h Treatment of isolated islets with a GIP/alanine mixture to induce glucagon secretion. Perifused islets isolated from control and α-GsKO mice were treated with a combination of GIP (10 nM) and alanine (3 mM) at G12. KCl (30 mM) was added at the end of the experiment (n = 4 mice per group). Note that GIP- and GIP/alanine-induced glucagon secretion was virtually abolished in α-GsKO islets. AOC values were calculated for different stimulation periods. All experiments were carried out with male littermates (14–20 weeks old). Blood was collected from the tail vein. Data are given as means ± SEM (in vitro studies: 4 perifusions with 75–100 islets per perifusion chamber). Data were analyzed via two-way repeated measures ANOVA for time with Bonferroni post hoc test for comparison of time (a, c, d–f) or two-tailed Student’s t test (AOC values in (h)). Numbers above the horizontal lines in the bar graphs represent p values. AOC, area of the curve. Source data are provided as a Source Data file.