Diabetic Csf1 mice lacking macrophages are protected against the development of delayed gastric emptying

Diabetic gastroparesis is associated with changes in interstitial cells of Cajal (ICC), neurons and smooth muscle cells in both animal models and humans. Macrophages appear to be critical to the development of cellular damage that leads to delayed gastric emptying but the mechanisms involved are not well understood. Csf1 (Op/Op) mice lack biologically active Csf1, resulting in the absence of Csf1-dependent tissue macrophages. The aim of this study was to use Csf1 mice to determine the role of macrophages in the development of delayed gastric emptying.

Animals were injected with streptozotocin to make them diabetic. Gastric emptying was determined weekly. Immunohistochemistry was used to identify macrophages and ICC networks in the gastric muscular layers. Oxidative stress was measured by serum malondialdehyde (MDA) levels. Quantitative, reverse transcription PCR was used to measure levels of mRNA.

Csf1 mice had normal ICC. With onset of diabetes both Csf1 and wild type Csf1 mice developed increased levels of oxidative stress (75.8 ± 9.1 and 41.2±13.6 nmol/mL MDA respectively). Wild type Csf1 mice developed delayed gastric emptying after onset of diabetes (4/13) whereas no diabetic Csf1 mouse developed delayed gastric emptying (0/15, P=0.035). ICC were disrupted in diabetic wild type Csf1 mice with delayed gastric emptying but remained normal in diabetic Csf1 mice.

Cellular injury and development of delayed gastric emptying in diabetes requires the presence of muscle layer macrophages. Targeting macrophages may be an effective therapeutic option to prevent cellular damage and development of delayed gastric emptying in diabetes.