Thus, in the present study, we investigated whether 1) acute intraperitoneal administration of GLP-1 (7–36) activates hypothalamic neurons through hepatic afferent nerves in non-obese rats, 2) chronic GLP-1 (7–36) treatment affects β-cell mass and proliferation and glucose metabolism via hepatic afferent/pancreatic efferent nerves in high-fat diet (HFD)-induced obese rats with insulin resistance and increased β-cell proliferation, and 3) chronic administration of liraglutide, a GLP-1R agonist, also affects β-cell mass and proliferation and glucose metabolism in a similar manner. The gene discussed is GLP1R; the disease is Insulin resistance.