Utilizing the GLP-1 signaling system to treat diabetes: sorting through the pharmacologic approaches.
Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that promotes glucose homeostasis through the regulation of insulin and glucagon secretion, gastric emptying, and food intake. This spectrum of effects makes GLP-1 an attractive candidate for drug development. However, because GLP-1 is a small peptide with rapid metabolism in the circulation, its usefulness to treat patients is limited. However, GLP-1 mimetics that are resistant to degradation have been developed and are effective in lowering blood glucose in diabetic patients. A second strategy for harnessing GLP-1 therapeutically is to inhibit the metabolism of endogenous GLP-1; several orally available compounds are in clinical trials. These two new classes of drugs both enhance GLP-1 signaling but differ in several key characteristics that may lead to distinct roles in the treatment of diabetic patients.
D'Alessio
David A
DA
University of Cincinnati, Division of Endocrinology/Metabolism, ML 0547, Vontz Center, 3125 Eden Avenue, Cincinnati, OH 45220-0547, USA. dalessd@ucmail.uc.edu
Vahl
Torsten P
TP
D058892:Adenosine Deaminase Inhibitors; D003920:Diabetes Mellitus / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D015195:Drug Design; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000502:physiology* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D010455:Peptides / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists*; D015398:Signal Transduction / Q000502:physiology*; D014688:Venoms / Q000627:therapeutic use
D058892:Adenosine Deaminase Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D006023:Glycoproteins; D010455:Peptides; D011480:Protease Inhibitors; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4