Insulinotropic toxins as molecular probes for analysis of glucagon-likepeptide-1 receptor-mediated signal transduction in pancreatic beta-cells.
Cholera toxin, pertussis toxin, mastoparan, maitotoxin, and alpha-latrotoxin are complex protein or polyether-based toxins of bacterial, insect, or phytoplankton origin that act with high potency at the endocrine pancreas to stimulate secretion of insulin from beta-cells located in the islets of Langerhans. The remarkable insulinotropic properties of these toxins have attracted considerable attention by virtue of their use as selective molecular probes for analyses of beta-cell stimulus-secretion coupling. Targets of the toxins include heptahelical cell surface receptors, GTP-binding proteins, ion channels, Ca(2+) stores, and the exocytotic secretory apparatus. Here we review the value of insulinotropic toxins from the perspective of their established use in the study of signal transduction pathways activated by the blood glucose-lowering hormone glucagon-like peptide-1 (GLP-1). Our analysis of one insulinotropic toxin (alpha-latrotoxin) leads us to conclude that there exists a process of molecular mimicry whereby the 'lock and key'analogy inherent to hormone-receptor interactions is reproduced by a toxin related in structure to GLP-1.
Holz
G G
GG
Department of Physiology and Neuroscience, Medical Sciences Building Room 442, New York University School of Medicine, 550 First Avenue, NY New York 10016, USA. holzg01@popmail.med.nyu.edu
Leech
C A
CA
Habener
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008387:Marine Toxins / Q000494:pharmacology; D008969:Molecular Sequence Data; D035964:Oxocins; D010455:Peptides; D037342:Pertussis Toxin; D018027:Receptors, Glucagon / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013111:Spider Venoms / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D000095702:Polyether Toxins
D002772:Cholera Toxin; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008387:Marine Toxins; D035964:Oxocins; D010455:Peptides; D037342:Pertussis Toxin; D018027:Receptors, Glucagon; D013111:Spider Venoms; D014118:Toxins, Biological; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; C000593833:GLP1R protein, human; C020763:alpha-latrotoxin; C037500:mastoparan; C020394:maitotoxin; D000095702:Polyether Toxins