Oral myo-inositol decreases gastrocnemius muscle glucose in European starlings<i>(Sturnus vulgaris)</i>with higher body mass but does not induce hypoglycemia

Background: Birds are unique as they maintain health despite naturally high glucose concentrations. Pilot data show that myo-inositol (MI) enhances fat metabolism in birds and may regulate fuel selection in tissues. We wondered whether MI regulates glucose in insectivorous birds. Objective: To understand how MI impacts blood glucose and tissue uptake in insectivorous birds. Hypotheses: Oral glucose with MI will lower blood and raise tissue glucose concentrations in wild-caught European starlings. Methods: Adult European starlings ( Sturnus vulgaris ) of both sexes were caught at a local park using mist nets and walk-in funnel traps and were brought to the Department of Animal Care and Technology at Arizona State University in Tempe, Arizona. Birds had ad libitum access to water and a nutritionally balanced diet of peas, corn, canned beans, Mazuri softbill diet, live mealworms, and ground pet food. Birds were given perches, plastic and paper balls, and mirrors and were acclimated at 75°F with a 12-hour light/dark schedule for two weeks. Whole blood glucose was measured with a veterinary glucometer on a drop of ulnar vein blood collected from 12-hour fasted birds before, 30, and 60 minutes following oral glucose (2 g/kg body mass) with or without co-administration of 5% MI. In the final study, fasted birds ate two mealworms and were given 2 g/kg oral glucose and 13C-glucose tracer with or without 5% MI. After 45 minutes, ulnar vein blood was collected, and birds were euthanized by CO 2 asphyxiation. Blood, liver, kidney, pectoralis, and gastrocnemius muscles were analyzed via targeted LC-MS metabolomics. Results: Two-way repeated measures ANOVA showed significant increases in blood glucose during the oral glucose tolerance test (p&lt;0.001). The combined effect of body mass and MI treatment on blood glucose showed that MI is hypoglycemic in heavier birds. Two-way ANOVA with treatment and body mass as factors showed a significant effect of body mass on tissue glucose (p=0.016). Student-Newman-Keuls (SNK) analyses showed that larger birds had ~1.3 times higher liver glucose compared to smaller birds (p=0.014) following oral glucose. Significant overall treatment effects (p=0.013) in gastrocnemius muscles with SNK post hoc analyses showed ~1.5 times lower glucose in birds with higher body mass following oral MI (p=0.019). MI increased liver glucose in heavier birds, suggestive of excess storage as glycogen. In contrast, MI decreased glucose in the gastrocnemius muscle of heavier birds, suggesting a shift to fat utilization for energy in this postural muscle. In summary, MI alters avian glucose metabolism in a body mass-dependent manner. A JumpStart grant from the Arizona State University Graduate &amp; Professional Student Association (M.S.) and a Human Frontiers Science Program postdoctoral fellowship (A.D.). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.