Pramlintide
Encyclopedia
Pramlintide acetate is a relatively new adjunct for diabetes
(both type 1 and 2), developed by Amylin Pharmaceuticals
.
, a small peptide hormone
that is released into the blood
stream by the β-cells
of the pancreas
along with insulin
, after a meal. Like insulin, amylin is deficient in individuals with diabetes.
By augmenting endogenous amylin, pramlintide aids in the absorption of glucose
by slowing gastric emptying
, promoting satiety via hypothalamic
receptors (different receptors than for GLP-1), and inhibiting inappropriate secretion of glucagon
, a catabolic hormone that opposes the effects of insulin and amylin.
ogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is not amyloidogenic (but would presumably retain clinical activity). Proline residues are known to be structure-breaking residues, so these were directly grafted into the human sequence.
Amino acid sequences:
Pramlintide (positively charged) is delivered as an acetate salt.
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
(both type 1 and 2), developed by Amylin Pharmaceuticals
Amylin Pharmaceuticals
Amylin Pharmaceuticals is a biopharmaceutical company based in San Diego, CA, that was founded in 1987. The company is engaged in the discovery, development and commercialization of drug candidates for the treatment of diabetes, obesity and other diseases. Currently, Amylin produces two drugs,...
.
Pharmacology
Pramlintide is an analogue of amylinAmylin
Amylin, or Islet Amyloid Polypeptide , is a 37-residue peptide hormone secreted by pancreatic β-cells at the same time as insulin .-Clinical significance:...
, a small peptide hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that is released into the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
stream by the β-cells
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
along with insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, after a meal. Like insulin, amylin is deficient in individuals with diabetes.
By augmenting endogenous amylin, pramlintide aids in the absorption of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
by slowing gastric emptying
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
, promoting satiety via hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
receptors (different receptors than for GLP-1), and inhibiting inappropriate secretion of glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
, a catabolic hormone that opposes the effects of insulin and amylin.
Approval
Symlin has been approved by the FDA, for use by Type 1 and Type 2 Diabetics who use insulin. Symlin allows patients to use less insulin, lowers average blood sugar levels, and substantially reduces what otherwise would be a large unhealthy rise in blood sugar that occurs in diabetics right after eating. Apart from insulin analogs, symlin is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin in the early 1920s.Design and structure
Since native human amylin is highly amyloidAmyloid
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...
ogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is not amyloidogenic (but would presumably retain clinical activity). Proline residues are known to be structure-breaking residues, so these were directly grafted into the human sequence.
Amino acid sequences:
Pramlintide: KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-(NH2)
Amylin: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-(NH2)
Rat amylin: KCNTATCATQRLANFLVRSSNNFGPVLPPTNVGSNTY-(NH2)
Pramlintide (positively charged) is delivered as an acetate salt.
External links
- www.symlin.com - product website
- www.amylin.com - Symlin page on the Amylin Pharmaceuticals website