Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels.
Glucose dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone synthesized in duodenal and jejunal enteroendocrine k cells in the proximal small bowel.
Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism.
Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans.
They slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake.
The two main molecules that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide).
Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Both GLP-1 and GIP are members of the glucagon peptide superfamily.
Gastrointestinal peptides that affect glycemic control.
Neuroendocrine cells, called L cells, mostly in large intestine produce GIP.
Incretins include amylin, gastric inhibitory peptide (GIP), and glucagon-like peptide 1 (GLP-1).
GIP levels increase minutes after eating.
GLP-1 causes insulin release from beta cell, but only when blood glucose levels are elevated.
Drugs that work through GLP-1 are less likely to cause hypoglycemia, unlike sulfonylureas which release insulin from the beta cells no matter the blood glucose levels.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that stimulates release following oral intake of glucose.
The effects of incretin hormones are diminished in patients with type II diabetes.
GLP-1 function is retained in type II diabetes and administration of GLP-one receptor agonists can restore the incretin effect in these patients.
Glucagon like peptide-1 (GLP-1) exists in two circulating equipotent molecular forms, GLP-1(&-37) and GLP-1(&-36)amide.
GLP-1 made in enteroendocrine L cells of the distal ileum and colon, and plasma levels increase in minutes after eating.
Hormones are released by the intestine throughout the day and are increased in response to a meal.
GLP-1 amplifies the effect of secreted insulin by decreasing glucagon.
GLP-1 slows gastric motility.
GLP-1 has a central effect on the hypothalamus on satiety and helps account for weight loss with incretins.
Incretin based medications are available in two families: DPP-4 inhibitors and GLP-1 receptor antagonists.
Several long-lasting GLP-1 analogs having insulinotropic activity have been developed, and several, including dulaglutide (Trulicity), exenatide (Byetta), liraglutide (Victoza), semaglutide (Ozempic, Wegovy and Rybelsus) and exenatide extended-release (Bydureon), have been approved.
Several DPP-4 inhibitors inhibit the enzyme that inactivates GLP-1 and GIP, and can be taken orally as tablets.
The incretin effect describes the phenomenon whereby oral glucose intake elicits a higher insulin response compared to intravenously introduced glucose that produces the same levels of serum glucose levels.