| 課程大綱 | Glucagon-like peptide-1 (GLP-1) is produced from the proglucagon gene in L cells of the small intestine and is secreted in response to nutrients. GLP-1 binds to a specific GLP-1 receptor, which is expressed in various tissues, including pancreatic beta cells, pancreatic ducts, gastric mucosa, kidney, lung, heart, skin, immune cells, and the hypothalamus. GLP-1 exerts its main effect by stimulating glucose-dependent insulin release from the pancreatic islets. It has also been shown to slow gastric emptying, inhibit inappropriate post-meal glucagon release, and reduce food intake. In patients with type 2 diabetes, there is an impaired insulin response to GLP-1, possibly related to a reduction in postprandial GLP-1 secretion or to other mechanisms. GLP-1 exhibits a short half-life of one to two minutes due to N-terminal degradation by the enzyme dipeptidyl peptidase-4 (DPP-4). This necessitates continuous infusion of GLP-1 to achieve steady-state levels in pharmacologic studies. Research has focused on GLP-1-like agonists that are resistant to DPP-4 degradation and on agents that increase GLP-1 via inhibition of DPP-4. Synthetic glucagon-like peptide-1 (GLP-1) receptor agonists are variably resistant to degradation by the enzyme dipeptidyl peptidase-4 (DPP-4) and therefore have a longer half-life, facilitating clinical use. They bind to the GLP-1 receptor and stimulate glucose-dependent insulin release from the pancreatic islets, as described above. They do not usually cause hypoglycemia in the absence of therapies that otherwise cause hypoglycemia. |
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