Incretins

Incretin mimetic Exenatide Mimic GLP-1C enhance prandial insulin secretion SC injectiond... 

The incretin effect is reduced in type 2 diabetes, and this is attributed, at least in part, to reduced secretion of GLP-1. The biological actions of GLP-1 remain essentially intact in type 2 diabetes, but administration of extra GLP-1 is not a practical therapeutic option because the peptide is degraded rapidly if A < 2 min) by the enzyme dipeptidyl peptidase IV (DPP-4). DPP-4 cleaves the N-terminal dipeptide from many of the peptides that have either an alanine or a proline residue penultimate to the N-terminus (Fig. 6). 

Antidiabetic Drugs other than Insulin. Table 3 Actions of the incretin hormones GIP (glucose-dependent insulinotropic polypeptide, gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1)... 

Incretin mimetic Severe renal or gastrointestinal disease Nausea, hypoglycaemia if used with another antidiabetic agent b... 

Glucose-dependent-insulinotropic peptide Incretin Hormones... 

Incretin Hormones Appetite Control Insulin Receptor... 

Incretins gut hormones that increase glucose-stimulated insulin secretion GLP-1 glucagon-like peptide-1 GDP Gastric inhibitory peptide or glucose-dependent insulino-tropic peptide... 

Incretin Hormones. Figure 2 The incretin effect. Patients underwent an oral or equivalent intravenous glucose load so that the glycemic profiles became similar. In such conditions, the data show that the oral glucose load is more potent to stimulate insulin secretion than an equivalent intravenous glucose stimulus. 

Incretin Hormones. Figure 3 Processing of the proglucagon. The proglucagon peptide is synthesized in pancreatic cells and cells from the gastrointestinal (Gl) tract and the brain. Different proconvertases process the peptide so that in the pancreas the glucagon is produced whereas in the Gl tract and the brain, the GLP-1 and GLP-2 peptides are mainly released. 

Importantly, both incretins when secreted by the intestine are rapidly degraded by the dipeptidyl peptidase IV (DPPFV), which removed the two amino-terminus histidine-alanine residues, thereby, inactivating the incretins. This enzyme is present at the surface of the epithelial intestinal cells and capillaries in the vicinity of the K and L cells secreting GIP and GLP-1, respectively. It is also present in the... 

In conclusion, the discovery of incretins has now come to an end in terms of therapeutic strategy of metabolic diseases since new medicines will be put on the market these coming years. However, a lot more needs to be done with regard to the physiological role of the hormones. Whereas the major filed of investigation for GLP-1 now relates to the effect of the peptide on the central nervous system and on (3-cell proliferation, for GIP it remains to understand its role in the numerous tissues where the corresponding receptor is expressed. 

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