Glucagon-producing cells are increased in Mas-deficient mice.

It has been shown that angiotensin(1-7) (Ang(1-7)) produces several effects related to glucose homeostasis. In this study, we aimed to investigate the effects of genetic deletion of Ang(1-7), the GPCR Mas, on the glucagon-producing cells. C57BL6/N Mas(-/-) mice presented a significant and marked increase in pancreatic alpha-cells (number of cells: 146 +/- 21 vs 67 +/- 8 in WT; P < 0.001) and the percentage per islet (17.9 +/- 0.91 vs 12.3 +/- 0.9% in WT; P < 0.0001) with subsequent reduction of +/--cells percentage (82.1 +/- 0.91 vs 87.7 +/- 0.9% in WT; P < 0.0001). Accordingly, glucagon plasma levels were increased (516.7 +/- 36.35 vs 390.8 +/- 56.45 pg/mL in WT; P < 0.05) and insulin plasma levels were decreased in C57BL6/N Mas(-/-) mice (0.25 +/- 0.01 vs 0.31 +/- 56.45 pg/mL in WT; P = 0.02). In order to eliminate the possibility of a background-related phenotype, we determined the number of glucagon-producing cells in FVB/N Mas-/-mice. In keeping with the observations in C57BL6/N Mas(-/-) mice, the number and percentage of pancreatic a-cells were also significantly increased in these mice (number of a-cells: 260 +/- 22 vs 156 +/- 12 in WT, P < 0.001; percentage per islet: 16 +/- 0.8 vs 10 +/- 0.5% in WT, P < 0.0001). These results suggest that Mas has a previously unexpected role on the pancreatic glucagon production.