Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus

Type 2 diabetes is associated with excessive food intake and a sedentary lifestyle. Local inflammation of white adipose tissue induces cytokine-mediated insulin resistance of adipocytes. This results in enhanced lipolysis within these cells. The fatty acids that are released into the cytosol can be removed by mitochondrial β-oxidation. The flux through this pathway is normally limited by the rate of ADP supply, which in turn is determined by the metabolic activity of the adipocyte. It is expected that the latter does not adapt to an increased rate of lipolysis. We propose that elevated fatty acid concentrations in the cytosol of adipocytes induce mitochondrial uncoupling and thereby allow mitochondria to remove much larger amounts of fatty acids. By this, release of fatty acids out of adipocytes into the circulation is prevented. When the rate of fatty acid release into the cytosol exceeds the β-oxidation capacity, cytosolic fatty acid concentrations increase and induce mitochondrial toxicity. This results in a decrease in β-oxidation capacity and the entry of fatty acids into the circulation. Unless these released fatty acids are removed by mitochondrial oxidation in active muscles, these fatty acids result in ectopic triacylglycerol deposits, induction of insulin resistance, beta cell damage and diabetes. Thiazolidinediones improve mitochondrial function within adipocytes and may in this way alleviate the burden imposed by the excessive fat accumulation associated with the metabolic syndrome. Thus, the number and activity of mitochondria within adipocytes contribute to the threshold at which fatty acids are released into the circulation, leading to insulin resistance and type 2 diabetes

Location of the Sources of 19 Mc/s Solar Bursts

By using large aerials in a new way, it has been possible to locate, with considerable accuracy, the sources of 19 Mcls solar bursts. The positions of these sources have been correlated with the positions of optically active regions associated with them, and the radial distances of the radio sources from the centre of the Sun have been deduced. In 1950-1951, 18�3 Mcls bursts came from sources at a radial distance estimated as 3�4Ro ; more reliable data in 1957 indicated that the sources of 19�7 Mcls bursts were at a radial distance of 2� 9Ro It is thought that these measurements give the distances of the fundamental plasma levels in coronal streamers.</jats:p

Observations of Cosmic Noise at 9·15 Mc/s

From observations made at a frequency of 9� 15 Mc/s, with an aerial of beam width 29� between half-power points and directed to Dec. -32�, a curve of equivalent aerial temperature, as a function of sidereal time, is derived.</jats:p

Observations of the General Background and Discrete Sources of 18·3 Mc/s Cosmic Noise

A survey of a broad strip of the sky, centred on Dec. ?32�, has been made at a frequency of 18�3 Mc/s using an aerial with an overall beam width to half-power of 17�. Previous results concerning the background distribution of brightness have been confirmed and 37 discrete sources have been detected. The distribution of these sources shows some galactic concentration ; it becomes homogeneous if sources within 18� of the galactic plane are excluded.</jats:p

A High Resolution Galactic Survey at 19·7 Mc/s

An extensive strip of the Southern Milky Way has been surveyed at 19� 7 Mc/s, using a Mills Cross with a pencil beam 1� 40 wide. The radio contours show a number of dark areas whose positions agree with those of optically-observed H II regions which at this frequency are soon in absorption. In addition, an intensity minimum along the galactic equator appears to represent the effect of absorption due to many H II regions extending to great distances in the galactic plane.</jats:p

In vitro Assessment of Tissue Damage Following Insertion of Micromachined Neural Prosthetic Devices

Supported in part by NIH, NIBIB, R01-EB00359, NINDS, R01-NS044287, NSF, ECR, EEC-9986821, and MicroBrightField Inc

Chronic Cellular Reactions to Silicon Neural Probe Implant

Chronic use of micromachined silicon neural probes is limited due to the formation of a complex sheath of cells and extracellular proteins that electrically isolates devices from adjacent neurons and neuronal damage. Understanding device-tissue interactions in the brain will provide a basis for developing successful interface strategies for biocompatible microdevices. While the reactive responses to single shank silicon devices inserted into neocortex are well characterized, responses in other regions have not been described. This study was designed to determine if the reactive responses observed in hippocampus and thalamus are similar to those observed in neocortex. This information is necessary to design and implement appropriate intervention strategies to control regional cell and tissue responses. Study of responses in hippocampus and thalamus has important scientific and clinical implications.This work was supported by the International Collaboration Program, NBS-ERC (Nano Bioelectronics and Systems Engineering Research Center)/ KOSEF (Korea Science and Engineering Foundation) and also supported in part by the Nanobiotechnology Center (NBTC), an STC Program of the National Science Foundation under Agreement No. ECS-9876771