The physiology and pharmacology of incretins in type 2 diabetes mellitus
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Two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1, help control blood glucose levels by affecting plasma insulin levels in response to oral glucose intake - this is known as the incretin effect. Incretins increase plasma insulin by a number of mechanisms, most of which are mediated through GIP and GLP-1 receptors (GIPR and GLP-1R respectively). Incretins act through the pancreas to stimulate insulin release and can also act at the cellular level by increasing insulin gene transcription and insulin biosynthesis. Incretins can also lower plasma glucose through non-insulin routes including inhibition of gastric emptying and reduced food intake. In type 2 diabetes, the incretin effect is reduced; as a result, insulin secretion is reduced and plasma glucose levels rise. However, the incretin effect can be restored in such individuals by the administration of exogenous incretins. Intravenous GLP-1 can stimulate insulin secretion, reduce glucagon secretion and normalize fasting plasma glucose in individuals with type 2 diabetes who were previously poorly controlled. The therapeutic potential of such agents is currently being explored.
|Journal||Diabetes, Obesity and Metabolism|
|Issue number||Suppl. 3|
|Number of pages||7|
|Publication status||Published - 2008|
incretins • pharmacology • physiology • type 2 diabetes