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There is a significant difference between the insulin secretory response to oral glucose compared with the response to intravenous glucose – a phenomenon known as the ‘incretin effect’ (Figure 5.13). The incretin effect is mediated by gut‐derived hormones, released in response to the ingestion of food, which augment glucose‐stimulated insulin release. In particular, there are two incretin hormones: glucagon‐like peptide‐1 (GLP‐1) and gastric inhibitory polypeptide (GIP). Both augment insulin secretion in a dose‐dependent fashion. GLP‐1 is secreted by L cells and GIP is secreted by K cells in the wall of the upper jejunum.

Figure 5.14 (a) The incretin effect is greatly diminished in patients with type 2 diabetes compared with normal subjects. This contributes to the impaired insulin secretory response observed in type 2 diabetes. (b) GLP‐1 has a trophic effect on pancreatic islets. Shown here is an islet from a db/db mouse before (left) and after (right) 2 weeks treatment with synthetic GLP‐1.

Adapted from Stoffers et al. Diabetes 2000; 49: 741–748.

In patients with type 2 diabetes, GLP‐1 secretion is diminished (Figure 5.14). However, in contrast to GIP, GLP‐1 retains most of its insulinotropic activity. GIP secretion is maintained in type 2 diabetes, but its effect on the β cell is greatly reduced.

GLP‐1 also suppresses glucagon secretion from pancreatic α cells and exerts additional effects on satiety and gastric emptying. There is also considerable interest in the trophic effects of GLP‐1 on β cells.