Pramlintide

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Pramlintide acetate (Symlin) is a relatively new adjunct treatment for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals. It is derived from amylin, a hormone that is released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes.

By substituting for amylin, pramlintide aids in the absorption of glucose by slowing gastric emptying, promoting satiety, and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin.

Symlin has been approved for use by the FDA by type 1 and type 2 diabetics who use insulin. Symlin results in weight loss, 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. Symlin is the only drug approved by the FDA to lower blood sugar in type 1 diabetics since insulin's discovery in the early 1920s.

Since native human amylin is highly amyloidogenic 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. The glutamine residue was also substituted with an asparagine, probably because glutamines are generally considered to be amyloid-promoting.

Amino acid sequences:

Pramlintide: KCNTATCATNRLANFLVHSSNNFGPILPPTNVGSNTY-(NH₂) Amylin: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-(NH₂) Rat amylin: KCNTATCATQRLANFLVRSSNNFGPVLPPTNVGSNTY-(NH₂)

Pramlintide (positively charged) is delivered as an acetate salt.