Tissue regeneration is thought to represent an evolutionary tradeoff that involves balancing energy resources among competing life history traits, such as body condition and repair. The Insulin and Insulin-like Signaling (IIS) network regulates physiological processes including growth, metabolism, reproduction, and wound healing, but its role in mediating energetic constraints on regeneration remains poorly understood. Using the brown anole lizard (Anolis sagrei), we tested the hypotheses that (1) increasing energetic deficit would progressively constrain tail regeneration and (2) supplemental insulin-like growth factors (IGF1 or IGF2) would mitigate this energetic constraint. Lizards were assigned to either an ad libitum or diet-restricted feeding regime prior to tail autotomy. Diet-restricted animals received subcutaneous injections of saline, IGF1, or IGF2 throughout regeneration. Regenerative growth and body mass were measured weekly for eight weeks. Greater body mass loss was increasingly associated with reduced regeneration over time, demonstrating a progressive energetic trade-off between body condition and regenerative performance. IGF1 did not alter this relationship. In contrast, IGF2 progressively buffered the negative effects of energetic deficit on regeneration, ultimately reversing the relationship between body mass loss and regenerative growth by the later stages of regeneration. Importantly, IGF2-treated animals did not lose less body mass than other diet-restricted animals, indicating that enhanced regeneration was not attributable to improved energetic state. Instead, IGF2 altered how regeneration responded to energetic limitation. These findings identify IGF2 as a regulator of the energetic trade-off underlying tissue regeneration and suggest that insulin-like signaling can modify regenerative performance without broadly altering whole-body energy balance.

Analysis Performed in the Publication of "What Influences Firearm Owners’ Storage Decisions? A National Survey of Barriers, Motivators, and Alternative Safety Strategies"