This study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes.

No abstract

BackgroundThe BRAFV600E mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A methylation, the regulatory mechanisms of RASSF1A-MST1 pathways remain to be elucidated, and the functional cooperation or cross regulation between BRAFV600E and MST1,which activates Foxo3,has not been investigated.Methodology/Principal FindingsThe negative regulators of the cell cycle, p21 and p27, are strongly induced by transcriptional activation of FoxO3 in BRAFV600E positive thyroid cancer cells. The FoxO3 transactivation is augmented by RASSF1A and the MST1 signaling pathway. Interestingly, introduction of BRAFV600Emarkedly abolished FoxO3 transactivation and resulted in the suppression of p21 and p27 expression. The suppression of FoxO3 transactivation by BRAFV600Eis strongly increased by coexpression of MST1 but it is not observed in the cells in which MST1, but not MST2,is silenced. Mechanistically, BRAFV600Ewas able to bind to the C-terminal region of MST1 and resulted in the suppression of MST1 kinase activities. The induction of the G1-checkpoint CDK inhibitors, p21 and p27,by the RASSF1A-MST1-FoxO3 pathway facilitates cellular apoptosis, whereasaddition of BRAFV600E inhibits the apoptotic processes through the inactivation of MST1. Transgenic induction of BRAFV600Ein the thyroid gland results in cancers resembling human papillary thyroid cancers. The development of BRAFV600Etransgenic mice with the MST1 knockout background showed that these mice had abundant foci of poorly differentiated carcinomas and large areas without follicular architecture or colloid formation.Conclusions/SignificanceThe results of this study revealed that the oncogenic effect of BRAFV600E is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAFV600E tumors.

PurposeChemerin has been suggested to be linked to insulin resistance and type 2 diabetes mellitus (T2DM). However, the relationship between visceral adiposity and chemerin levels remains unclear in subjects with T2DM. In this study, we investigated the relationship between serum chemerin levels and visceral adiposity.Materials and MethodsThis study included 102 subjects newly diagnosed with T2DM. The relationships between serum chemerin levels and clinical and biochemical parameters were examined. Multiple linear regression analysis was performed to determine the predictable factors of serum chemerin levels.ResultsSerum chemerin levels showed significant positive correlations with body mass index (BMI), waist circumference (WC), visceral fat thickness (VFT), insulin levels, the homeostasis model assessment of insulin resistance, and levels of triglycerides (log-transformed) and high-sensitivity C-reactive protein, while showing significant negative correlations with high-density lipoprotein cholesterol. After adjusting for BMI and WC, VFT showed a significant relationship with serum chemerin levels (r=0.222, p=0.027). Moreover, VFT was an independent predictive factor of serum chemerin levels (β=0.242, p=0.041).ConclusionWe demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM.