High-Performance Air-Stable n-Channel Organic Thin Film Transistors Based on Halogenated Perylene Bisimide Semiconductors

The syntheses and comprehensive characterization of 14 organic semiconductors based on perylene bisimide (PBI) dyes that are equipped with up to four halogen substituents in the bay area of the perylene core and five different highly fluorinated imide substituents are described. The influence of the substituents on the LUMO level and the solid state packing of PBIs was examined by cyclic voltammetry and single crystal structure analyses of seven PBI derivatives, respectively. Top-contact/bottom-gate organic thin film transistor (OTFT) devices were constructed by vacuum deposition of these PBIs on SiO2 gate dielectrics that had been pretrearted with n-octadecyl triethoxysilane in vapor phase (OTS-V) or solution phase (OTS-S). The electrical characterization of all devices was accomplished in a nitrogen atmosphere as well as in air, and the structural features of thin films were explored by grazing incidence X-ray diffraction (GIXD) and atomic force microscopy (AFM). Several of those PBIs that bear only hydrogen or up to two fluorine substitutents at the concomitantly flat PBI core afforded excellent n-channel transistors, in particular, on OTS-S substrate and even in air (mu > 0.5 cm(2) V-1 s(-1); I-on/I-off > 10(6)). The best OTFTs were obtained for 2,2,3,3,4,4,4-heptafluorobutyl-substituted PBI 1a ("PTCDI-C4F7") on OTS-S with n-channel field effect mobilities consistently > 1 cm(2) V-1 s(-1) and on-to-off current rations of 10(6) in a nitrogen atmosphere and in air. For distorted core-tetrahalogenated (fluorine, chlorine, or bromine) PBIs, less advantageous solid state packing properties were found and high performance OTFTs were obtained from only one tetrachlorinated derivative (2d on OTS-S). The excellent on-to-off current modulation combined with high mobility in air makes these PBIs suitable for a wide range of practical applications.X11442428sciescopu

The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling

Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and cholesterol content in the livers of PKD3-deficient mice fed a high-fat diet. Conversely, hepatic-specific overexpression of a constitutively active PKD3 mutant suppressed insulin-induced signaling and caused insulin resistance. Our results indicate that PKD3 provides feedback on hepatic lipid production and suppresses insulin signaling. Therefore, manipulation of PKD3 activity could be used to decrease hepatic lipid content or improve hepatic insulin sensitivity

Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity

Nutrient overload in combination with decreased energy dissipation promotes obesity and diabetes. Obesity results in a hormonal imbalance, which among others, activates G-protein coupled receptors utilizing diacylglycerol (DAG) as secondary messenger. Protein kinase D1 (PKD1) is a DAG effector which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP-activated protein kinase (AMPK)-dependent manner. Moreover, mice lacking PKD1 in adipocytes are resistant to diet-induced obesity due to elevated energy expenditure. Beiging of adipocytes promotes energy expenditure and counteracts obesity. Consistently, deletion of PKD1 promotes expression of the β3-adrenergic receptor (ADRB3) in a CCAAT/enhancerbinding protein (C/EBP)-α and δ-dependent manner, which leads to the elevated expression of beige markers in adipocytes and subcutaneous adipose tissue. Finally, deletion of PKD1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, loss of PKD1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications

Platelet‐derived lipids promote insulin secretion of pancreatic β cells

Abstract Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that platelets may play a role in the regulation of metabolism. Pancreatic β cells are the central regulators of systemic glucose homeostasis. Here, we show that factor(s) derived from β cells stimulate platelet activity and platelets selectively localize to the vascular endothelium of pancreatic islets. Both depletion of platelets and ablation of major platelet adhesion or activation pathways consistently resulted in impaired glucose tolerance and decreased circulating insulin levels. Furthermore, we found platelet‐derived lipid classes to promote insulin secretion and identified 20‐Hydroxyeicosatetraenoic acid (20‐HETE) as the main factor promoting β cells function. Finally, we demonstrate that the levels of platelet‐derived 20‐HETE decline with age and that this parallels with reduced impact of platelets on β cell function. Our findings identify an unexpected function of platelets in the regulation of insulin secretion and glucose metabolism, which promotes metabolic fitness in young individuals