Nandini Avula

O-GlcNAcylation is a post-translational modification that involves the attachment of N-acetylglucosamine to target proteins by the enzyme O-GlcNAc transferase (OGT). This modification can change a protein’s function, activity, and cellular interactions. Previous research suggests that OGT may play a vital role in the inflammatory response associated with acute pancreatitis (AP) development. In this study, we hypothesized that OGT regulates pancreatic inflammation indirectly by changing the O-GlcNAcylation state of the proinflammatory transcription factor Nf-κb. To test this hypothesis, we induced acute pancreatitis via caerulein injection in heterozygous OGT (OGT-Het, expressing 50% OGT compared to control) mice models and control mice. Pancreatic tissues were assessed for AP severity via morphometry. Moreover, serum was collected to detect the presence of inflammatory cytokines (IL-1⍺, IL-1β, IL-6, and TNF-⍺) and digestive enzymes (lipase and amylase). Since obesity and hyperglycemia can produce worse outcomes in pancreatitis, we established that there are no significant differences in body weight and blood glucose between Pdx OGT f/+ and controls. Additionally, caerulein treatment generated an appropriate model to study pancreatitis as indicated by elevated pancreas weight/ body weight ratio, edema, and inflammatory infiltrate scores. Preliminary results also suggest that partial OGT loss may not be sufficient to produce apparent histological differences in AP severity, but sample size is small.