immediately passes the pouch and enters the so-called alimentary limp of the Y and finally
the common limp, where it meets the digestive juices. This presents nutrients to more distal
parts of the small intestine, where the L-cell density is higher. This results in a grossly
exaggerated secretion of GLP-1 as shown in the figure
The response may be 30 fold greater than in non-operated controls exposed to the same
meal. The L-cells also hypersecrete PYY, which does not seem to influence glucose metabolism,
but which is potently anorexic. Together these two hormones may explain the loss of appetite
and thereby the reduction in food intake, observed postoperatively. Plasma glucose concentrations
also rise rapidly because of an accelerated absorption of glucose and together with the
exaggerated GLP-1 secretion it is no wonder that insulin secretion is also increased.
In fact, the insulin secretion pattern may appear completely normal after the operation.
The increase is seen already a week after the operation and remains 3 months and
1 year as shown in the figure. In fact it lasts for many years, together with the exaggerated
GLP-1 response. It has been proven that it actually is the increase in GLP-1 secretion
that is responsible for the augmented insulin secretion, because the augmentation is completely
lost if the patients are given an antagonist of the GLP-1 receptor. Because of the increased
insulin secretion, deposition of glucose in muscle and fat is
also greatly accelerated, and this is the immediate cause of the improved glucose tolerance.
With time and as the patient loses weight, ectopic fat is removed also from the muscles
and therefore, the peripheral insulin sensitivity is also improved. So the diabetes resolution
is caused by an increased secretion of insulin caused by gut hormones and an improved insulin
sensitivity, caused by energy restriction and weight loss.
There may be other factors involved, and there are many details that I haven’t dealt with,
but there is little doubt that these are the essential features.
Therefore one the main research challenges in this field for the coming years will be
to find out exactly how the exaggerated secretion of the gut hormones is brought about. If we
knew that, we might be able to induce a similar hypersecretion without the operation. Naturally