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Figure 1. The incretin hormones and glucose homeostasis. Adapted from Drucker, 2006. 2

Incretin hormones stimulate insulin release from pancreatic β-cells in a
glucose-dependent manner (i.e. the insulin release happens only when
glucose concentrations are normal or elevated, as typically observed
in response to glucose ingestion); therefore the glucose-lowering effect
they elicit does not result in hypoglycaemia. There is even evidence to
suggest that GLP-1 may stimulate increases in β-cell mass and function;
attributes we’ll consider later in this chapter. 4 5

The incretin effect and T2DM

Several abnormalities have been observed in the entero-insular axis in
T2DM patients. These defects include:
6

7 8
z Reduced GLP-1 response to food (Figure 2). This has not been uniformly
confirmed, the majority of studies showing unchanged GLP-1 secretion
comparing T2DM patients and healthy control subjects (Figure 3).
9
z A somewhat decreased potency of GLP-1 in stimulating the release of insulin
(Figure 3). However, exogenous GLP can still lower glucose concentrations
10
into the normal range in patients with T2DM.
z An almost complete loss of insulin secretion in response to even high doses
of GIP. 11 12
z Suppression of glucagon secretion is impaired during oral glucose tolerance
tests (OGTTs) as opposed to isoglycaemic intravenous glucose infusion.
13
This is also true in healthy subjects, so it is not an abnormality in T2DM.
14

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