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

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

In vitro Assessments of Vascular Damage and Tissue Deformation Following the Insertion of Silicon Neural Probe

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