Abstract
The pancreatic islets of Langerhans, which are composed of α, β, δ, ε, and PP cells, orchestrate systemic glucose homeostasis through tightly regulated hormone secretion. Although the precise mechanisms involving β cells in the onset and progression of diabetes have been elucidated and insulin replacement therapy remains the primary treatment modality, the regulatory processes, functions, and specific roles of other pancreatic islet hormones in diabetes continue to be the subject of ongoing investigation. At present, a comprehensive review of the secretion and regulation of pancreatic islet cell hormones as well as the related mechanisms of diabetes is lacking. This review synthesizes current knowledge on the secretion mechanisms of insulin, glucagon, somatostatin, ghrelin, and pancreatic polypeptides, emphasizing their functional crosstalk in diabetes. Emerging advances include CRISPR-based β-cell regeneration, bioengineered islet transplantation, and bioelectronic interventions aimed at restoring pancreatic function. Future research directions highlight artificial intelligence-guided prediction of hormone dynamics, therapeutics targeting the gut microbiome-islet axis, and tissue-engineered artificial islets. By integrating mechanistic insights, physiological roles, and translational innovations, this review outlines precision strategies for targeting islet hormone networks, offering a roadmap toward restoring metabolic equilibrium in diabetes.