Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes

• Published in: Islets Vol. 4; no. 2; pp. 173 - 176
• Main Authors: Tiano, Joseph P., Mauvais-Jarvis, Franck
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.03.2012; Landes Bioscience
• Subjects: Addendum; Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line; Cycle; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - prevention & control; estrogen receptor; Female; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; islet; Landes; lipogenesis; Mice; Organogenesis; Proteins; Raloxifene Hydrochloride - pharmacology; Receptors, Estrogen - metabolism; Selective Estrogen Receptor Modulators - pharmacology; STAT3 Transcription Factor - metabolism; Triglycerides - metabolism; type 2 diabetes; β-cell
• ISSN: 1938-2014; 1938-2022
• DOI: 10.4161/isl.19747

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.