Pancreatic Islet Cell Crosstalk: Insight Into α‐/β‐Cell Compensatory Mechanisms

islets. This functional rebalancing is consistent with an adaptive response to emerging β-cell dysfunction. Functional assays demonstrated that insulin secretion in prediabetic islets became increasingly reliant on glucagon-driven potentiation of GLP-1R and cAMP-dependent pathways. Transcriptomic and signaling data confirmed enhanced expression of cAMP-related intermediates and calcium-handling components, indicating partial preservation of insulin secretory capacity despite underlying defects. α-cell remodeling and flexible engagement of glucagon and GLP-1 receptors act as key compensatory mechanisms that may help to sustain insulin secretion during early β-cell stress. The context-dependent plasticity of intra-islet receptor activation highlights a coordinated multicellular adaptation in prediabetes and suggests that targeting intra-islet endocrine crosstalk may help preserve β-cell function in prediabetes.