Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

Madhusudan Grover, Surendra Dasari, Cheryl E. Bernard, Lakshmikanth L. Chikkamenahalli, Katherine P. Yates, Pankaj J. Pasricha, Irene Sarosiek, Richard McCallum, Kenneth L. Koch, Thomas L. Abell, Braden Kuo, Robert J. Shulman, Simon J. Gibbons, Travis J. McKenzie, Todd A. Kellogg, Michael L. Kendrick, James Tonascia, Frank A. Hamilton, Henry P. Parkman, Gianrico Farrugia

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Macrophagebased immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with proinflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 x 10-9; IG FDR = 6.3 x 10-12]. In DG, properdin expression correlated with GCSI bloating (r = -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-type, and complement C2 correlated with 4 h gastric retention (r = -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophagedriven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis.

Original languageEnglish (US)
Pages (from-to)G716-G726
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5
StatePublished - Nov 2019


  • Diabetes
  • Immune cells
  • Inflammation
  • Macrophages

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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