Hormone-based therapies in the regulation of fuel metabolism and body weight.
BACKGROUND
The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes.


OBJECTIVE
To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes.


METHODS
Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed.


CONCLUSIONS
In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.
Kesty
Nicole C
NC
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, USA. nicole.kesty@amylin.com
Roth
Jonathan D
JD
Maggs
David
D
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004734:Energy Metabolism; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D006706:Homeostasis; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D020738:Leptin / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism
D052242:Adiponectin; D000682:Amyloid; D006728:Hormones; D058228:Islet Amyloid Polypeptide; D020738:Leptin; D052216:Glucagon-Like Peptide 1; C105254:pramlintide