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Friday, November 28, 2014

Incretin Effect

What is incretin?

As Incretin the central part of the 1960s described is referred to in medicine that at the same blood sugar levels intravenous injection of glucose leads to a significantly lower distribution of hypoglycemic hormone insulin as an oral glucose supply. Therefore, the concentration of glucose in the blood does not explain alone the amount of insulin the pancreas. Mid-1980s, the extent of the incretin effect was estimated as a function of the amount of glucose to about 25 to 60 percent of the insulin response on the basis of experimental data.

Cause of the incretin effect

The cause of the Incretin the existence of hormones has been postulated to be formed by the intestines. Looking for these hormones called incretins first the glucose-dependent formed by the K cells of duodenal mucosa insulinotropic peptide (GIP) was found, its insulin-releasing activity was detected in 1970. However, since neutralization of the GIP reduces the incretin effect by only 20 to 50 percent, Searched for further Inkretinen. Mid-1980s, the glucagon-like peptide 1 was then described (GLP-1), which is produced by the L-cells of the intestinal mucosa. The highest density of these cells can be found at the end of the small intestine, known as the ileum and the beginning of the large intestine called the cecum. It was shown that GLP-1 has a significant share of the incretin effect and that its effect is additive to the effect of GIP. At present, it is assumed that these two hormones are responsible for the entire Incretin.

Clinical Application

Based on detailed analysis of GIP and GLP-1 was attempting to develop systems based on these hormones or their regulatory mechanisms medications for the treatment of type 2 diabetes mellitus.

GIP was found that for a high blood sugar level has no stimulatory effect on insulin release. GLP-1 effect in diabetics is indeed lower than in metabolically healthy people, but enough for a hypoglycemic effect. GLP-1 itself proved to be in a medical application due to degradation by the enzyme dipeptidyl peptidase 4 as too unstable and thus as to short-term in its effect.

However, other substances have been found which are not subject to this enzymatic cleavage and show comparable with the effect of GLP-1 to its receptor due to structural similarities. These substances are called incretin mimetics. Lead compound of this new class is exenatide. It is the synthetic version of a hormone as exendin-4 in the saliva of the Gila monster (Heloderma suspectum), an American lizard was found. Another class of drugs based on the incretin effect are the inhibitors of dipeptidyl peptidase-4, the delay due to inhibition of dipeptidyl peptidase-4 degradation of endogenous GLP-1.

For both classes of drugs was found that their effect is due to a stimulation of the release of insulin and glucagon inhibition of secretion and that their use reduces the blood sugar fasting and after food intake. Exenatide for a reduction in body weight was detected beyond. In addition, evidence was found in other studies that long-term treatment with incretin mimetics and dipeptidyl peptidase-4 inhibitors may protect the insulin-producing beta cells and prevent their destruction or at least delayed. The effect of both drug classes also depends on the blood glucose levels, so that, in contrast to the other approved anti-diabetic drugs, there is virtually no risk of hypoglycaemia.

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