The insulin/IGF receptor puzzle in pancreatic β-cell recovery: a missing link for diabetes therapy?

Pancreatic β cells maintain glucose homeostasis through insulin production, and their loss underlies both type 1 and type 2 diabetes. Among the signaling systems that govern β-cell biology, insulin and insulin-like growth factor (IGF) receptor pathways have long attracted attention as intrinsic modulators of β-cell growth, survival, and secretory competence. However, the physiological and pathological relevance of these receptors in β cells remains uncertain, reflecting model-specific discrepancies and the complex interplay between local autocrine and systemic endocrine effects. Recent analyses have expanded this view, revealing the coexistence of insulin receptor-dependent and insulin receptor-independent regulatory modules that govern β-cell adaptation to metabolic stress. Furthermore, molecular regulators, including inceptor and IGF2R, reshape our understanding of insulin/IGF receptor signaling as a flexible, adaptive network. Together, these insights suggest that precise modulation of receptor networks may hold the key to unlocking endogenous β-cell regenerative capacity.