Resident - Small Animal Internal Medicine Cornell University Ithaca, New York, United States
Abstract: Background – Glucagon helps maintain glucose and amino acid homeostasis but may be dysregulated in disease states. Increased plasma glucagon reduces plasma amino acids, may increase urinary amino acid clearance, acts as an insulin secretagogue, and modulates cellular metabolism.
Hypothesis/Objectives – Exogenous glucagon significantly alters the canine plasma metabolome.
Animals – Five healthy male purpose-bred research beagles.
Methods – Two 6-hour glucagon infusions were performed, a low-dose CRI (3 ng/kg/min; CRI-LO) and a high-dose CRI (50 ng/kg/min; CRI-HI), with a 7-day washout in between. A continuous flash glucose system monitored interstitial glucose. Untargeted liquid chromatography-mass spectrometry (LC-MS) was performed on plasma samples collected before and after infusions. Data were analyzed with MetaboAnalyst.
Results – A transient increase (peak 90-120 min) in glucose occurred during the CRI-HI but not CRI-LO. Glucose levels returned to near baseline by the end of the 6-hour infusion. The CRI-LO significantly changed 372 plasma metabolites, with 333 metabolites reduced. The CRI-HI significantly affected 414 metabolites, with 369 reduced. Generally, changes were in the same direction under both conditions and were reflected by distinct clustering of post-CRI metabolites (Figure 1) by data-reduction (sPLS-DA). The CRI-HI broadly reduced circulating amino acid levels, especially arginine and proline. Other affected pathways included purine, pyrimidine, arachidonic acid, and primary bile acid biosynthesis (Table 1).
Conclusions and clinical importance – Exogenous glucagon significantly alters the canine plasma metabolome independently of glucose levels. These data will aid our understanding of glucagon physiology and the pathophysiology of canine disorders involving glucagon.
