Incretin is a hormonal agent that stimulates insulin secretion in action to meals. The two essential incretin hormonal agents are called glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Understanding how these hormones work is assisting to yield new treatments for Type 1 and Type 2 diabetes.
The entire concept of incretin hormones originates from a decades-old observation that orally administered glucose provokes a far greater release of insulin than the same amount of glucose provided by injection. Researchers postulated that there should be some signal from the gastrointestinal tract (or “gut”) that increases insulin release whenever food is consumed. A significant amount of evidence now recommends that GLP-1 and GIP are accountable for most of this increased insulin release. Moreover, researchers have actually also observed that people with Type 2 diabetes have diminished insulin release in action to meals and have actually speculated that they may have problems in the release or action of their incretin hormones.
GLP-1 is made in the small intestine and colon and is launched in reaction to food. It promotes insulin secretion in a glucose-dependent manner — that is, it promotes insulin secretion just when there is glucose in the blood stream. GLP-1 has other advantageous effects as well: It postpones stomach emptying, which slows the absorption of carbohydrate and the resulting rise in blood sugar level after meals; it curbs cravings; and animal studies have revealed that it might promote regrowth of the pancreatic beta cells and battle apoptosis (programmed cell death), improving the survival of existing beta cells.
See also: Hormones Affecting Blood Glucose Levels
GIP is made by cells in the upper small intestine and is launched when glucose comes in contact with these cells. Like GLP-1, GIP affects the pancreatic beta cells, where it stimulates insulin secretion, and also appears to promote beta cell expansion and beta cell survival.
Naturally, all these results have prompted drug companies and medical scientists to create drugs that act like incretin hormones or affect their biochemical pathways. For example, they have discovered a compound in Gila monster venom called exendin-4, which acts similarly to human GLP-1 however is much longer-acting. Amylin Pharmaceuticals and Eli Lilly and Company developed an artificial variation of exendin-4 called exenatide (brand name Byetta), which got marketing approval in April of 2005 as an adjunctive treatment for Type 2 diabetes that is not effectively controlled by metformin, a sulfonylurea drug (such as glyburide, glipizide, or glimepiride), or both. The makers also established Bydureon, a formulation of exenatide that needs to be injected just as soon as a week instead of twice a day. Novo Nordisk has produced liraglutide (Victoza), a GLP-1 analog for individuals with Type 2 diabetes that is injected once a day, and a variety of other drug business likewise have GLP-1 analogs under advancement.
Researchers have actually tried instilling GIP into individuals with Type 2 diabetes, with differing outcomes. In some cases, insulin secretion was increased, however in others, little or no extra insulin was secreted at all.
Another class of drugs called DPP-IV inhibitors also affect incretin hormonal agent levels. Dipeptidyl peptidase IV (or DPP-IV) is an enzyme that normally breaks down GLP-1 and GIP. DPP-IV inhibitors, which obstruct the action of this enzyme and therefore leave more of the body’s own GLP-1 and GIP in circulation. DPP-IV inhibitors, that include sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta), have been revealed to enhance blood glucose control, enhance the insulin secretory reaction, and boost insulin sensitivity.