Muscle Adaptations to Hyperglycemia Enable Nectar Bats to Thrive on a Sugar-Rich Diet

Nectar-feeding bats, often referred to as "hummingbirds of the night," thrive on sugar-rich diets that induce extreme postprandial hyperglycemia exceeding 750 mg/dL, levels intolerable for most mammals. To investigate the metabolic adaptations underlying this resilience, we compared closely related bat species with divergent diets using RNA sequencing of muscle tissue, proteomic analyses from serum samples, and physiological studies focusing on glucose and insulin dynamics. Functional ex vivo muscle experiments reveal insulin resistance in nectar bats, with diminished pAKT activation despite high circulating glucose levels. However, these bats exhibit insulin-independent glucose uptake, facilitated by muscle contractions and alternative glucose transporters, alongside muscle-specific expression of gck (glucokinase), which supports rapid glucose metabolism. Muscle tissue in nectar bats also shows increased triglyceride storage, indicating that excess glucose is directed toward fat production rather than glycogen storage. Additional adaptations include differential mTOR expression, contributing to metabolic flexibility and energy utilization for flight. Unlike other mammals with insulin resistance, nectar bats lack substantial adipose tissue, underscoring the central role of muscle in postprandial glucose regulation. These findings provide a comprehensive view of how nectar bats achieve metabolic resilience, offering novel insights into mammalian adaptations to extreme dietary pressures. Supported by NSF Postdoctoral Fellowship #2109717, BWF Diversity Enrichment Program #G-1022339, and HHMI Hanna H. Gray Fellowship #GT-15991 to J.C. 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.