Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though 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 SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that 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. Based on 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-0880/-/DC1.
- Received July 19, 2016.
- Accepted February 7, 2017.
- © 2017 by the American Diabetes Association.