Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications.
Amylin receptor agonism is emerging as part of an integrated neurohormonal therapeutic approach for managing diabetes mellitus (DM) and body weight. Pramlintide acetate, an analogue of the pancreatic hormone amylin, has been studied in the United States as an antihyperglycemic agent in patients with type 1 or type 2 DM treated with mealtime insulin(1). Further clinical testing of pramlintide in subjects with obesity demonstrated that pramlintide monotherapy induced significant, sustained, and dose-dependent weight loss(2). Recent clinical observations point to its compatibility as a combination therapy with the hormone leptin, eliciting double-digit weight loss in patients with overweight and obesity(3). Herein, we link amylin activation of central neural circuits to these therapeutic effects, and we speculate on other potential therapeutic applications of amylin receptor agonism.
Roth
Jonathan D
JD
Amylin Pharmaceuticals, Inc, San Diego, CA 92121, USA. jonathan.roth@amylin.com
Maier
Holly
H
Chen
Steve
S
Roland
Barbara L
BL
D000682:Amyloid / Q000819:agonists / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000819:agonists* / Q000502:physiology
D000682:Amyloid; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide