Pramlintide


Pramlintide is an injectable amylin analogue drug for diabetes, developed by Amylin Pharmaceuticals. Pramlintide is sold as an acetate salt.

Pharmacology

Pramlintide is an analogue of amylin, a small peptide hormone that is released into the bloodstream by the β cells of the pancreas 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 by slowing gastric emptying, promoting satiety via hypothalamic receptors, 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.

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 amyloidogenic and potentially toxic, the strategy for designing pramlintide was to substitute residues from rat amylin, which is less amyloidogenic although not completely
. 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:
PramlintideKCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-
AmylinKCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-
Rat amylinKCNTATCATQRLANFLVRSSNNLGPVLPPTNVGSNTY-

Pramlintide as protein is.