TAT peptide

The purpose of this study was to evaluate adipose tissue distributions and hepatic and pancreatic fat contents using a 6-point Dixon MRI technique in type 2 diabetes mellitus (T2DM), and to assess associations between fat distributions and biochemical markers of insulin resistance. Intra-abdominal MRI was investigated in 14 T2DM patients, 13 age- and sex-matched healthy controls (HC) and 11 young HC using a 3 T Prisma MRI scanner. All T2DM subjects completed a fasting comprehensive metabolic panel, and demographic measurements were taken according to standardized methodologies. We observed excellent correlation (R-2 = 0.94) between hepatic fat fraction quantified using 6-point Dixon MRI and gold standard MRS, establishing the accuracy and reliability of the Dixon technique. Significantly increased visceral adipose tissue (VAT) volumes were found in T2DM patients compared to age-matched HC (1569.81 +/- 670.62 cm(3) vs. 1106.60 +/- 566.85 cm(3), p = .04). We also observed a trend of increasing subcutaneous adipose tissues (SAT), and total abdominal fat (TAT) volumes in T2DM compared to age-matched HC. Hepatic fat fraction percentage (HFF%) was 44.6% higher in T2DM compared to age-matched HC and 64.4% higher compared to young HC. Pancreatic fat fractions in the head and body/tail were higher in T2DM patients compared to both healthy cohorts. We also observed correlations between fat contents of the liver and pancreas in T2DM patients, and association between biochemical markers of T2DM with HFF, indicating a risk for non-alcoholic fatty liver disease among T2DM. In summary, this study provides evidence of T2DM patients having increased liver and pancreatic fat, as well as increased adipose tissues.

We report the glutathione-triggered release of an anticancer drug from vesicles constructed with peptide amphiphiles (PAs) containing a cell-penetrating TAT peptide synthesized by varying the position and number of disulfide-linkages in the PAs. PAs 1 and 2, based on random-coil structures that enable large amounts of drug loading, showed different self-assembled aggregates. These included vesicles and two-dimensional sheets as functions of the cysteine (C) position in the PA, despite the use of the same chemical building blocks. However, the formation of C-C disulfide-bridges between neighboring PAs by sonication in polar-aprotic solvent, dimethylformamide led to morphological changes into the vesicles. Interestingly, the PA vesicles demonstrated markedly different drug loading capacities and efficiencies as functions of the disulfide position during assembly. Increases in the number of disulfide formations between PAs (1-1) allowed the vesicular drug transporter to exhibit sustained anticancer-drug release to specific tumors. As all vesicles reported in this study exhibited a superior ability to deliver anticancer drugs to certain cancer cells alone, this research, which provides a biocompatible peptide design for the synthesis of efficient drug-delivery vehicles, can serve as a solid foundation for further nanocarrier developments for biomedical applications.