title: Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes.
abstract: We recently showed that the female hormone 17β-estradiol (E2) protects against β-cell failure in rodent models of type 2 diabetes (T2D) by suppressing islet fatty acids and glycerolipids synthesis, thus preventing lipotoxic β-cell failure. E2 anti-lipogenic actions were recapitulated by pharmacological activation of the estrogen receptor (ER)α, ERβ and the G-protein coupled ER (GPER) in cultured rodent and human β-cells. In vivo, in mouse islets, ERα activation inhibited β-cell lipogenesis by suppressing fatty acid synthase expression (and activity) via an extranuclear, estrogen response element (ERE)-independent pathway requiring the signal transducer and activator of transcription 3. Here, we show that in INS-1 insulin-secreting cells, the selective ER modulator (SERM), Raloxifene, behaves both as ER antagonist with regard to nuclear ERE-dependent actions and as an ER agonist with regard to suppressing triglyceride accumulation. This additional finding opens the perspective that SERMs harboring ER agonistic activity in β-cells could have application in postmenopausal prevention of T2D. Additional studies using novel generation SERMs are needed to address this issue.
authors.affiliation: Department of Medicine, Division of Endocrinology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tiano
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
mesh_terms: D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; D020845:Selective Estrogen Receptor Modulators; C494087:Stat3 protein, mouse; D014280:Triglycerides; D020849:Raloxifene Hydrochloride