title: Identification and Functional Implications of Sodium/Myo-Inositol Cotransporter 1 in Pancreatic β-Cells and Type 2 Diabetes.
abstract: Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, although the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and, specifically, β-cells. Genetic or pharmacological inhibition of SMIT1 impaired glucose-stimulated insulin secretion by INS-1E cells, probably via downregulation of PI signaling. In addition, SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions. In corroboration, chronic MI treatment improved the disease phenotypes of diabetic rats and islets. On the basis of our results, we postulate that the MI transporter SMIT1 is required to maintain a stable PI pool in β-cells in order that PI remains available despite its rapid turnover.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Stephen Yu Ting
authors.initials: SYT
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Sam Tsz Wai
authors.initials: STW
authors.lastname: Cheng
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China psleung@cuhk.edu.hk.
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006943:Hyperglycemia; D007150:Immunohistochemistry; D007294:Inositol / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010695:Phlorhizin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D027981:Symporters / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D027981:Symporters; C571821:sodium-myo-inositol cotransporter, rat; D007294:Inositol; D010695:Phlorhizin