GIP Role in Metabolism, Glucose Homeostasis and Diabetes

Glucose-dependent insulinotropic polypeptide (GIP) has emerged as a critical mediator in the complex interplay between the gastrointestinal tract, metabolic regulation, and systemic glucose homeostasis. While the incretin effect and the role of other gastrointestinal (GI) hormones have received extensive attention, GIP’s paramount importance—constituting 60%–80% of the postprandial insulin response—has only recently gained recognition for its pivotal contribution to both normal and pathological nutrient deposition. Novel insights reveal that the mechanisms through which GIP exerts its influence extend well beyond the GI tract, encompassing significant expression of GIP receptors and ligands within the central nervous system and modulating neural, metabolic, and cognitive functions. Despite ongoing investigation, several questions remain regarding the precise physiology of GIP and its contribution to the etiology of type 2 diabetes mellitus (T2DM) and related metabolic disorders.Recent studies have highlighted the multifaceted roles of GIP, including the modulation of insulin release through both direct and indirect pathways, promoting neural progenitor proliferation, and affecting bone, cardiac, and intestinal function. Moreover, the redundancy and synergy between GIP and insulin, once vital for survival in nutrient-scarce environments, have now been implicated in the maladaptation seen with caloric surplus—catalyzing the progression to T2DM and obesity. However, significant gaps remain in our understanding of the full spectrum of GIP’s metabolic actions, including its effects in the brain and its role in appetite regulation, as well as its potential as a therapeutic target in metabolic disease.This Research Topic aims to advance a comprehensive understanding of the physiological properties of GIP in the regulation of metabolism and in the pathogenesis of T2DM and other nutrient-related disorders. It seeks to clarify the mechanisms involved in modulating the enteroinsular axis, elucidate its crosstalk with insulin, and dissect its systemic and central effects. By fostering discussion among leading researchers, the collection aspires to address unresolved questions, encourage novel hypotheses, and propel the translation of foundational science to clinical innovation in metabolic disease management.The scope of this Research Topic includes original research, reviews, perspectives, and commentary that investigate the breadth of GIP effects on metabolism and in disease. Submissions should address, but are not limited to, the following themes:- GIP and its signaling pathways in gastrointestinal and extraintestinal tissues- The interaction of GIP with insulin and other incretins in glucose homeostasis- GIP’s effects on neural function, cognitive health, and appetite regulation- The contribution of GIP to the pathophysiology of T2DM, obesity, and metabolic abnormalities, including metabolic dysfunction-associated fatty liver disease (MAFLD) and the metabolic syndrome- Effects of GIP on bone, the myocardium, and nutrient transport/absorption- Therapeutic implications of targeting GIP and related pathways in metabolic disorders Topic editors: Michael Wolfe, Victor Alan Gault Source: https://www.frontiersin.org/research-topics/78147/gip-role-in-metabolism-glucose-homeostasis-and-diabetes