Disrupted Insulin Signaling Due to an Acute Immune Response in Swine
Authors: Markley Grace , Cooper Elizabeth , Stahl Chad , Palou Egoaguirre Rousset , Budke Brennan , Burdon Reece 
Published: May 2024

Insulin is an anabolic hormone involved in glucose uptake and synthesis of fats, proteins, and glycogen. Altered insulin signaling can occur due to metabolic state, pathogen exposure, and autoimmune disorders. Lipopolysaccharide (LPS), an endotoxin secreted produced by gram-negative bacteria, can induce a severe, systemic immune response. In pigs, chronic LPS exposure has induced insulin resistance. However, the effects of acute exposure to LPS on insulin signaling and resistance has not been elucidated. Crossbred nursery pigs (58, 12.1 kg ± 0.23kg BW) were randomly assigned into two experimental subsets, where 10 animals were designated for repeated blood sampling and 48 animals underwent timed euthanasia for tissue collection. For repeated blood sampling, jugular catheters were placed under anesthesia and the animals were given 48 hours to recover before being randomly assigned to treatments. These treatments were an intraperitoneal injection of either 15μg/kg BW LPS or an equal volume of 0.9% Saline (n=5 pigs/treatment). Blood was collected for 48 hours followed by euthanasia. The other 48 pigs were randomly assigned to the same treatments, and then randomly assigned to euthanasia timepoints of 0, 3, 6, 12, 24 or 48 hours post injection for tissue collection. Among the catheterized pigs, two hours post LPS challenge there was a decrease in serum insulin concentration (p<0.05) and mild hyperglycemia (p<0.05) post challenge. At 12 and 24 hours post LPS challenge there was a decrease in insulin (p<0.05) and a trend hyperglycemia was also apparent at 24 hours (p=0.063). In liver tissue, insulin related genes exhibited alterations post LPS injection. Phosphoinositide 3-kinase ( pi3k) and insulin receptor substrate 1 ( irs1) expression were decreased at 3 and 6 hours (p<0.05) and protein kinase b ( akt) expression were decreased at 3 hours (p<0.05) post challenge. The expression of insulin inhibitor growth factor receptor bound protein 10 ( grb10) was decreased at 6, 12, and 24 hours after challenge (p<0.05). Fructose-1-6-bisphosphatase ( f16bp) expression was reduced at 3, 6, and 12 hours (p<0.05) in the liver while phosphoenolpyruvate carboxykinase ( pepck) expression was decreased at 3 and 6 hours (p<0.01) post challenge. Other metabolic genes were decreased at 3, 6, and 12 hours post LPS challenge, including fatty acid synthase ( fas) (p<0.05), carbohydrate response element binding protein ( chrebp) (p<0.05), and acetyl CoA carboxylase ( acc)(p<0.05). Protein abundance of Akt 3 hours after LPS injection was decreased in the liver (p<0.05). In skeletal muscle 6 hours post LPS injection, insulin receptor ( insr), insulin-like growth factor receptor ( igfr) and fas were all increased (p<0.05) These results indicate disrupted insulin signaling at various levels after an acute immune response. Research reported in this abstract was supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) of the National Institutes of Health under award number R01HD092304A. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.