摘要The glucagon receptor(GCGR)is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus(T2DM)and obesity.Activation of GCGR enhances systemic in-sulin sensitivity through paracrine stimulation of insulin secretion,presenting a promising avenue for treatment.However,the discovery of effective GCGR agonists remains a challen-ging and resource-intensive process,often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds.Recent advances in artificial intelligence techno-logies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity.In the present work,we propose DeepGCGR,a two-layer deep learning model that leverages graph convolutional networks(GCN)integrated with a multiple attention mechanism to expedite the identification of GCGR agonists.In the first layer,the model predicts the bioactivity of various compounds against GCGR,efficiently filtering large chemical libraries to identify promising candidates.In the second layer,Deep-GCGR classifies high bioactive compounds based on their functional effects on GCGR signaling,identifying those with potential agonistic or antagonistic effects.Moreover,DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine(TCM).The proposed meth-od will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.