Glucagon-like peptides.
Proglucagon contains the sequence of two glucagon-like peptides, GLP-1 and GLP-2, secreted from enteroendocrine cells of the small and large intestine. GLP-1 lowers blood glucose in both NIDDM and IDDM patients and may be therapeutically useful for treatment of patients with diabetes. GLP-1 regulates blood glucose via stimulation of glucose-dependent insulin secretion, inhibition of gastric emptying, and inhibition of glucagon secretion. GLP-1 may also regulate glycogen synthesis in adipose tissue and muscle; however, the mechanism for these peripheral effects remains unclear. GLP-1 is produced in the brain, and intracerebroventricular GLP-1 in rodents is a potent inhibitor of food and water intake. The short duration of action of GLP-1 may be accounted for in part by the enzyme dipeptidyl peptidase 4 (DPP-IV), which cleaves GLP-1 at the NH2-terminus; hence GLP-1 analogs or the lizard peptide exendin-4 that are resistant to DPP-IV cleavage may be more potent GLP-1 molecules in vivo. GLP-2 has recently been shown to display intestinal growth factor activity in rodents, raising the possibility that GLP-2 may be therapeutically useful for enhancement of mucosal regeneration in patients with intestinal disease. This review discusses recent advances in our understanding of the biological activity of the glucagon-like peptides.
Drucker
D J
DJ
Department of Medicine, the Toronto Hospital, Banting and Best Diabetes Centre, University of Toronto, Ontario, Canada. d.drucker@utoronto.ca
D000595:Amino Acid Sequence; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005934:Glucagon / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018027:Receptors, Glucagon
C000593833:GLP1R protein, human; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon