Incretin effect: difference between revisions
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| 10 | In healthy adults, the incretin effect accounts for approximately 50–70% of the total insulin secretion that follows oral glucose intake. The remaining 30–50% comes from direct stimulation of beta cells by the rising blood glucose itself, termed the glucose-stimulated response. This dual-mechanism design — nutrient-sensing via hormones, plus direct glucose sensing — confers tight glycaemic control in the postprandial state while minimizing the risk of hypoglycaemia when glucose is low.{{r|holst2007}} | 10 | In healthy adults, the incretin effect accounts for approximately 50–70% of the total insulin secretion that follows oral glucose intake. The remaining 30–50% comes from direct stimulation of beta cells by the rising blood glucose itself, termed the glucose-stimulated response. This dual-mechanism design — nutrient-sensing via hormones, plus direct glucose sensing — confers tight glycaemic control in the postprandial state while minimizing the risk of hypoglycaemia when glucose is low.{{r|holst2007}} |
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| + | 12 | In type 2 diabetes, the incretin effect is markedly reduced, accounting for only 10–30% of the insulin secretory response. This defect is a primary lesion in the pathophysiology of the disease and is the mechanistic rationale for [[GLP-1 receptor agonist|GLP-1-directed]] and [[Dual incretin agonist|dual-agonist]] therapeutics, which restore or amplify this pathway.{{r|nauck2018}} | |
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| 12 | == Historical discovery == | 14 | == Historical discovery == |
| 13 | The observation that oral glucose intake provokes a larger insulin response than intravenous glucose at matched glycaemic levels was documented in the 1920s, but the mechanism was unknown for over 40 years. Early hypotheses included a direct effect of the intestinal mucosa on the pancreas (Loewi's "enteroinsular axis") and nervous reflexes, but these remained speculative until the insulin-secreting peptide hormones of the gut were isolated and characterized.{{r|creutzfeldt1979}} | 15 | The observation that oral glucose intake provokes a larger insulin response than intravenous glucose at matched glycaemic levels was documented in the 1920s, but the mechanism was unknown for over 40 years. Early hypotheses included a direct effect of the intestinal mucosa on the pancreas (Loewi's "enteroinsular axis") and nervous reflexes, but these remained speculative until the insulin-secreting peptide hormones of the gut were isolated and characterized.{{r|creutzfeldt1979}} |
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| + | 17 | Glucagon, isolated in 1923, was the first gut hormone to be recognised, but its insulinotropic effect is glucose-independent and was therefore insufficient to explain the oral-glucose phenomenon. The isolation and characterization of GLP-1 (in the early 1980s) and the demonstration of its glucose-dependent insulinotropic properties resolved the question. GIP, previously known only as a gastric-inhibitory peptide, was subsequently recognised to be the second arm of the incretin axis.{{r|holst1987}} | |
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| 15 | == References == | 19 | == References == |
| 16 | {{reflist}} | 20 | {{reflist}} |
| 17 | <ref name="creutzfeldt1979">Creutzfeldt W, Ebert R, Willms B. "Gastro-intestinal peptide hormones and insulin secretion." ''Diabetologia'' 20 Suppl:85–98 (1979).</ref> | 21 | <ref name="creutzfeldt1979">Creutzfeldt W, Ebert R, Willms B. "Gastro-intestinal peptide hormones and insulin secretion." ''Diabetologia'' 20 Suppl:85–98 (1979).</ref> |
| 18 | <ref name="holst2007">Holst JJ. "The physiology of glucagon-like peptide 1." ''Physiological Reviews'' 87(4):1409–1439 (2007). DOI:10.1152/physrev.00034.2006. PMID 17928588.</ref> | 22 | <ref name="holst2007">Holst JJ. "The physiology of glucagon-like peptide 1." ''Physiological Reviews'' 87(4):1409–1439 (2007). DOI:10.1152/physrev.00034.2006. PMID 17928588.</ref> |
| + | 23 | <ref name="holst1987">Holst JJ, Ørskov C, Nielsen OV, Schwartz TW. "Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut." ''FEBS Letters'' 211(2):169–174 (1987). PMID 3542566.</ref> | |
| + | 24 | <ref name="nauck2018">Nauck MA, Meier JJ. "Incretin hormones: their role in health and disease." ''Diabetes, Obesity and Metabolism'' 20(Suppl 1):5–21 (2018). DOI:10.1111/dom.13129. PMID 29364588.</ref> | |
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| 20 | {{DEFAULTSORT:Incretin effect}} | 26 | {{DEFAULTSORT:Incretin effect}} |