title: Augmented glucose-induced insulin release in mice lacking G(o2), but not G(o1) or G(i) proteins.
abstract: Insulin secretion by pancreatic β cells is a complex and highly regulated process. Disruption of this process can lead to diabetes mellitus. One of the various pathways involved in the regulation of insulin secretion is the activation of heterotrimeric G proteins. Bordetella pertussis toxin (PTX) promotes insulin secretion, suggesting the involvement of one or more of three G(i) and/or two G(o) proteins as suppressors of insulin secretion from β cells. However, neither the mechanism of this inhibitory modulation of insulin secretion nor the identity of the G(i/o) proteins involved has been elucidated. Here we show that one of the two splice variants of G(o), G(o2), is a key player in the control of glucose-induced insulin secretion by β cells. Mice lacking G(o2)α, but not those lacking α subunits of either G(o1) or any G(i) proteins, handle glucose loads more efficiently than wild-type (WT) mice, and do so by increased glucose-induced insulin secretion. We thus provide unique genetic evidence that the G(o2) protein is a transducer in an inhibitory pathway that prevents damaging oversecretion of insulin.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Sangeun
authors.initials: S
authors.lastname: Park
authors.forename: Neil S
authors.initials: NS
authors.lastname: Bajpayee
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nagaoka
authors.forename: Guylain
authors.initials: G
authors.lastname: Boulay
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: Meisheng
authors.initials: M
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin; D020033:Protein Isoforms; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005947:Glucose