Aim: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.
Methods: Male imprinting control region (ICR) mice (4 wk old) were divided into two groups: control mice, and streptozotocin-induced diabetic mice. Eight weeks after injection, spontaneous gastric contraction was recorded by using physiography in control and streptozotocin-induced diabetic mice. The ANP-positive cells in gastric mucosa and among dispersed gastric epithelial cells were detected by using immunohistochemistry and flow cytometry, respectively. ANP and natriuretic peptide receptor type A (NPR-A) gene expression in gastric tissue was observed by using the reverse transcriptase polymerase chain reaction.
Results: The frequency of spontaneous gastric contraction was reduced from 12.9 +/- 0.8 cycles/min in the control group to 8.4 +/- 0.6 cycles/min in the diabetic mice (n = 8, P < 0.05). However, the amplitude of contraction was not significantly affected in the diabetic group. The depletion of interstitial cells of Cajal in the gastric muscle layer was observed in the diabetic mice. ANP-positive cells were distributed in the gastric mucosal layer and the density index of ANP-positive cells was increased from 20.9 +/- 2.2 cells/field in control mice to 51.8 +/- 2.9 cells/field in diabetic mice (n = 8, P < 0.05). The percentage of ANP-positive cells among the dispersed gastric epithelial cells was increased from 10.0% +/- 0.9% in the control mice to 41.2% +/- 1.0% in the diabetic mice (n = 3, P < 0.05). ANP and NPR-A genes were both expressed in mouse stomach, and the expression was significantly increased in the diabetic mice.
Conclusion: These results suggest that the ANP/NPR-A signaling pathway is upregulated in streptozotocin-induced diabetic mice, and contributes to the development of diabetic gastroparesis.