Sweet taste disorder and vascular complications in patients with abnormal glucose tolerance

AbstractBackgroundIt remains unknown whether taste disorders can be a risk factor for micro- and macro-vascular diseases in patients with abnormal glucose tolerance.MethodsA cross-sectional study in a nationally representative samples of 848 and 849 US adults (aged ≥40years) with diabetes or prediabetes who had sweet and salt taste disorders, respectively, from the National Health and Nutrition Examination Survey 2011–2012.ResultsAmong the study population, 5.7% had sweet taste disorder and 8.6% had salt taste disorder. These data correspond to approximately 1.5 million and 1.8 million individuals with abnormal glucose tolerance aged 40years or older in the US population, respectively. In the adjusted model, sweet taste disorder was significantly associated with complication of ischemic heart disease (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.03–5.81; P=0.04). Moreover, sweet taste disorder in patients with diabetes was significantly associated with diabetic retinopathy (adjusted OR, 2.89; 95% CI, 1.09–7.69; P=0.03) and diabetic nephropathy (adjusted OR, 3.17; 95% CI, 1.07–9.36; P=0.03). Meanwhile, salt taste disorder was not significantly associated with diabetic retinopathy, diabetic nephropathy, ischemic heart disease, or stroke. Total sugar intake was significantly higher in patients with sweet taste disorder than in those without it, whereas total daily intake of carbohydrate did not differ significantly. No significant association was observed between salt taste disorder and daily intake of sodium after multivariate analysis.ConclusionsSweet taste disorder in patients with abnormal glucose tolerance was associated with increased sugar intake and vascular complications

Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem cells. We previously reported that Msi1 contributes to the maintenance of the immature state and self-renewal activity of neural stem cells through translational repression of m-Numb. However, its translation repression mechanism has remained unclear. Here, we identify poly(A) binding protein (PABP) as an Msi1-binding protein, and find Msi1 competes with eIF4G for PABP binding. This competition inhibits translation initiation of Msi1's target mRNA. Indeed, deletion of the PABP-interacting domain in Msi1 abolishes its function. We demonstrate that Msi1 inhibits the assembly of the 80S, but not the 48S, ribosome complex. Consistent with these conclusions, Msi1 colocalizes with PABP and is recruited into stress granules, which contain the stalled preinitiation complex. However, Msi1 with mutations in two RNA recognition motifs fails to accumulate into stress granules. These results provide insight into the mechanism by which sequence-specific translational repression occurs in stem cells through the control of translation initiation