Abstract 555: Glucagon-producing Cells are Increased in Mas-deficient Mice
Glucagon is produced by the pancreatic α-cells and has an important role in diabetes. Genetic deletion of the angiotensin-(1-7)/receptor Mas is associated with metabolic disturbances. However, the role of Mas in the pancreatic morphology/function is not known. In the present study we investigated the number of pancreatic α-cells and indirectly β-cells number in C57BL/6J and FVB/N Mas-deficient (KO-Mas) mice. After overnight fasting, 12 weeks-old male KO-Mas mice were sacrificed by i.p. administration of ketamin/xylazine. The pancreas was dissected and the splenic part was fixed in formalin for immunohistochemistry analysis. Tissues were cut (5μm thick), with 150μm interval between cuts to obtain different pancreatic islets, and incubated with anti-glucagon primary antibody. Peroxidase activity was visualized by exposing the sections to DAB solution. Ten islets per mouse pancreas were randomly chosen and all the cells present in the islet were counted. After that, each marked α-cell was also counted using a light microscope. The estimated β-cell content was obtained subtracting the total cells from the α-cells. Mas-deficiency resulted in an increase in the number and percentage of the pancreatic α-cell in both backgrounds compared to wild-type mice (C57BL6/J number of α-cell: 146±21 vs. 67±8 in WT, p<0.001; percentage per islet: 17.9±0.91 vs. 12.3±0.9% in WT, p<0.0001; FVB/N number of α-cell: 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). The estimated β-cell number was not significantly different in both backgrounds. However the percentage of β-cells were reduced in both backgrounds (C57BL6/J: 82.1±0.91 vs. 87.7±0.9%, in WT p<0.0001; FVB/N: 83.53±1.2 vs. 88.6±0.9% in WT, p<0.001). No significant differences were observed in total amount of cells in pancreatic islets, although a trend for increase in Mas-KO was observed. These data suggest that the Mas/Ang-(1-7) axis is important for the maintenance of normal pancreatic morphology. The imbalance of α and β-cell in Mas-KO might be involved in the metabolic alterations produced by Mas deletion, in mice.
- © 2013 by American Heart Association, Inc.