Pramlintide (trade name Symlin) is an injectable

amylin Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by sl ...

analogue drug for

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

(both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includi ...

). Pramlintide is sold as an acetate salt.

Pharmacology

Pramlintide is an analogue of

, a small peptide

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

that is released into the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

stream by the β cells of the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...

along with insulin after a meal. Like insulin, amylin is completely absent in individuals with Type I diabetes. In synergy with endogenous amylin, pramlintide aids in the regulation of blood

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

by slowing gastric emptying, promoting satiety via hypothalamic receptors (different receptors than for

GLP-1 Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certa ...

), and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin. Pramlintide also has effects in raising the acute first-phase insulin response threshold following a meal. Both a reduction in glycated hemoglobin and weight loss have been shown in insulin-treated patients with type 2 diabetes taking pramlintide as an adjunctive therapy.

Research Applications

In the research field, pramlintide has been experimented with and used as a potential treatment drug. Pramlintide has demonstrated its ability to decrease amyloid beta plaques in Alzheimer's disease mouse models.

Approval

Pramlintide has been approved by the FDA, for use by type 1 and type 2 diabetic patients who use insulin. Pramlintide 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, pramlintide 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

amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the huma ...

ogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is less amyloidogenic although not completely (but would presumably retain clinical activity). Proline residues are known to be structure-breaking residues, so these were directly grafted into the human sequence. Despite its enhanced stability compared to human amylin, pramlintide is still able to organize into amyloid material. Amino acid sequences: Pramlintide as protein is (positively charged).

References

External links

www.symlin.com
- product website
www.amylin.com
- Symlin page on the Amylin Pharmaceuticals website {{Oral hypoglycemics and insulin analogs Anti-diabetic drugs Diabetes Human proteins AstraZeneca brands Recombinant proteins Peptide hormones