Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis.
GLP-1 (9-36)amide is the cleavage product of GLP-1(7-36) amide, formed by the action of diaminopeptidyl peptidase-4 (Dpp4), and is the major circulating form in plasma. Whereas GLP-1(7-36)amide stimulates glucose-dependent insulin secretion, GLP-1(9-36)amide has only weak partial insulinotropic agonist activities on the GLP-1 receptor, but suppresses hepatic glucose production, exerts antioxidant cardioprotective actions and reduces oxidative stress in vasculature tissues. These insulin-like activities suggest a role for GLP-1 (9-36)amide in the modulation of mitochondrial functions by mechanisms independent of the GLP-1 receptor. In this paper, we discuss the current literature suggesting that GLP-1(9-36)amide is an active peptide with important insulin-like actions. These findings have implications in nutrient assimilation, energy homeostasis, obesity, and the use of Dpp4 inhibitors for the treatment of diabetes.
Tomas
Eva
E
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA 02114, USA.
Habener
Joel F
JF
D000595:Amino Acid Sequence; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006321:Heart / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011972:Receptor, Insulin / Q000378:metabolism / Q000502:physiology*; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D011972:Receptor, Insulin