Physiologic gut-pancreas axis

The physiologic gut-pancreas axis, also known as the entero-insular axis, is a complex bidirectional communication network that coordinates the body's metabolic response to nutrient ingestion [1.2.1, 1.3.1]. It primarily involves the release of incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), from enteroendocrine cells in the gut in response to food [1.2.2, 1.2.5]. These hormones travel to the pancreatic islets to stimulate insulin secretion and inhibit glucagon release in a glucose-dependent manner, thereby maintaining glycemic homeostasis [1.2.4, 1.3.3]. Beyond hormonal signaling, the axis integrates neural pathways, such as the vagus nerve, and microbial metabolites like short-chain fatty acids to regulate pancreatic function and energy balance [1.1.4, 1.3.2]. Dysregulation of this axis is a hallmark of metabolic diseases like type 2 diabetes and obesity, making its components—particularly the GLP-1 and GIP receptors—highly successful therapeutic targets for modern metabolic pharmacology [1.1.2, 1.2.1].

Other names

Entero-insular axisGut-islet axisGut-pancreas axisIncretin axis

Modulation of the axis via GLP-1 receptor agonism, GIP receptor agonism, or inhibition of DPP-4-mediated incretin degradation to enhance insulin secretion and glucose homeostasis.