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Incretin effect: difference between revisions

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5| Magnitude in healthy adults = 50–70% of the total insulin secretory response to oral glucose5| Magnitude in healthy adults = 50–70% of the total insulin secretory response to oral glucose
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+7{{hatnote|For the hormones that mediate this effect, see [[Glucagon-like peptide-1]] and [[Glucose-dependent insulinotropic polypeptide]].}}
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8The '''incretin effect''' is the observation that oral intake of glucose evokes a substantially larger [[Insulin secretion|insulin secretory response]] than intravenous infusion of glucose at an identical glycaemic excursion. This difference was first documented in the early 20th century but was not explained until the 1960s, when two [[peptide]] hormones secreted by the small intestine — [[Glucagon-like peptide-1]] (GLP-1) and [[Glucose-dependent insulinotropic polypeptide]] (GIP) — were shown to potentiate insulin secretion in response to nutrients.{{r|creutzfeldt1979}}9The '''incretin effect''' is the observation that oral intake of glucose evokes a substantially larger [[Insulin secretion|insulin secretory response]] than intravenous infusion of glucose at an identical glycaemic excursion. This difference was first documented in the early 20th century but was not explained until the 1960s, when two [[peptide]] hormones secreted by the small intestine — [[Glucagon-like peptide-1]] (GLP-1) and [[Glucose-dependent insulinotropic polypeptide]] (GIP) — were shown to potentiate insulin secretion in response to nutrients.{{r|creutzfeldt1979}}
19== Mechanisms: GLP-1 and GIP ==20== Mechanisms: GLP-1 and GIP ==
20GLP-1 and GIP together account for the incretin effect through glucose-dependent potentiation of insulin secretion. Neither hormone stimulates insulin secretion at low glucose concentrations, a feature that minimizes hypoglycaemia risk compared to insulin secretagogues like sulfonylureas, which do so.{{r|holst2007}}21GLP-1 and GIP together account for the incretin effect through glucose-dependent potentiation of insulin secretion. Neither hormone stimulates insulin secretion at low glucose concentrations, a feature that minimizes hypoglycaemia risk compared to insulin secretagogues like sulfonylureas, which do so.{{r|holst2007}}
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+23GLP-1 is secreted by L cells of the distal small intestine and colon, in response to glucose, fat and amino acids. Its plasma half-life is approximately 2 minutes due to rapid inactivation by [[Dipeptidyl peptidase-4]]. GIP is secreted earlier, by K cells of the duodenum and proximal jejunum, and has a half-life of approximately 7 minutes. The two hormones act through distinct receptors on beta cells; both couple to adenylyl cyclase and raise intracellular cAMP, but through non-identical signalling cascades, and each contributes approximately equally to the total incretin effect in health.{{r|nauck2018}}
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22== References ==25== References ==