Glucose is the primary regulator of insulin secretion. High blood glucose (hyperglycemia) will induce insulin release. In contrast, low blood glucose will decrease insulin release.
The fed state will stimulate the production of incretin hormones, including GLP-1 and GIP. Oral glucose will trigger the secretion of insulin 2-3x more than intravenous glucose administration due to incretin hormone involvement. Insulin works by upregulating glycolysis and reducing gluconeogenesis.
GLP-1 (Glucagon-like Peptide-1) is an incretin hormone secreted by the colon and lower intestinal L cells after a meal, enhancing pancreatic beta cell sensitivity to glucose. It reduces glucagon secretion and delays gastric emptying. GLP-1 works by binding to cell surface receptors coupled with G protein-adenylyl cyclase system and is degraded by dipeptidyl peptidase-4 (DPP-4). GLP-1 increases glucose-dependent insulin release.
GIP (Gastric Inhibitory Polypeptide or Glucose-dependent Insulinotropic Polypeptide) is an incretin hormone secreted by upper small intestinal K cells. It inhibits gastric acid secretion and promotes insulin secretion.
The beta-2 receptor is present in pancreatic beta cells, and is responsible for stimulating insulin secretion. The beta-2-adrenergic receptor is a Gs protein-coupled receptor, which activates adenylyl cyclase and raises intracellular cAMP.
Muscarinic M3 receptors are part of the parasympathetic nervous system and can induce insulin secretion. The smell or scent of food can trigger these. The muscarinic-M3 receptor is a Gq protein-coupled receptor which activates adenylyl cyclase and raises intracellular cAMP.
The alpha-2 receptor is a part of the sympathetic system present in pancreatic beta cells and inhibits insulin secretion. It impacts the insulin axis more than other sympathetic receptors, including beta-2 receptors. The alpha-2 receptor is a Gi protein-coupled receptor.
Somatostatin is a hormone produced by the delta cells of the pancreas. It can suppress insulin and glucagon release. However, somatostatin suppresses insulin more than glucagon.
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