Incretins and the development of type 2 diabetes |
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Authors: | Juris J Meier MD Michael A Nauck MD |
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Institution: | (1) Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany |
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Abstract: | The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are released in response to
nutrient ingestion and potentiate glucosestimulated insulin secretion from pancreatic β cells. The augmentation of postprandial
insulin secretion by such gastrointestinal hormones is called the incretin effect. The incretin effect is almost completely
absent in patients with type 2 diabetes. This is due to 1) an approximate 15% reduction in postprandial GLP-1 secretion and
2) a near total loss of insulinotropic activity of GIP. This review article summarizes clinical studies on abnormalities in
the secretion and insulinotropic effects of GIP and GLP-1 in patients with type 2 diabetes as well as in individuals at high
risk. A significant proportion of first-degree relatives are characterized by a reduced insulinotropic response to exogenous
GIP. Nevertheless, this phenomenon does not predispose to a more rapid deterioration in glucose tolerance or conversion to
impaired glucose tolerance or diabetes. Therefore, although there are hints of early abnormalities in incretin secretion and
action in prediabetic populations, it has not been proven that such phenomena are central to the pathogenesis of type 2 diabetes. |
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