Mining incretin hormone pathways for novel therapies.
The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are produced predominantly by enteroendocrine cells and have multiple blood glucose-lowering effects. Recent years have seen a surge of interest in understanding the basic physiology and pathophysiology of incretins and in applying this knowledge to the treatment of diabetes and obesity. Considerable gains have been made in elucidating the mechanisms controlling incretin secretion, and there is growing evidence to suggest that incretins might be involved in the rapid reversal of diabetes observed in gastric bypass patients. Here, we review these recent advances and outline the multiple strategies being pursued to exploit the potential therapeutic benefits of GIP and GLP-1.
Wideman
Rhonda D
RD
Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Kieffer
Timothy J
TJ
D000818:Animals; D050110:Bariatric Surgery; D003920:Diabetes Mellitus / Q000628:therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors; D055808:Drug Discovery; D004435:Eating / Q000502:physiology; D019858:Enteroendocrine Cells / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents; D054795:Incretins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism; D018716:Molecular Mimicry; D009765:Obesity / Q000628:therapy
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1