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The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.
Numerical and experimental investigation of tensile behavior of laser beam welded TRIP700 steel
(2011)
The development and analysis of three waveguides for the exposure of small biological in vitro samples to mobile communication signals at 900 MHz (GSM, Global System for Mobile Communications), 1.8 GHz (GSM), and 2 GHz (UMTS, Universal Mobile Telecommunications System) is presented. The waveguides were based on a fin-line concept and the chamber containing the samples bathed in extracellular solution was placed onto two fins with a slot in between, where the exposure field concentrates. Measures were taken to allow for patch clamp recordings during radiofrequency (RF) exposure. The necessary power for the achievement of the maximum desired specific absorption rate (SAR) of 20 W/kg (average over the mass of the solution) was approximately Pin = 50 mW, Pin = 19 mW, and Pin = 18 mW for the 900 MHz, 1800 MHz, and 2 GHz devices, respectively. At 20 W/kg, a slight RF-induced temperature elevation in the solution of no more than 0.3 °C was detected, while no thermal offsets due to the electromagnetic exposure could be detected at the lower SAR settings (2, 0.2, and 0.02 W/kg). A deviation of 10% from the intended solution volume yielded a calculated SAR deviation of 8% from the desired value. A maximum ±10% variation in the local SAR could occur when the position of the patch clamp electrode was altered within the area where the cells to be investigated were located.
Modification and testing of an engine and fuel control system for a hydrogen fuelled gas turbine
(2011)
Meiotic functions of RAD18
(2011)