| 1. |
|
|
| 2. |
- Enoksson, Staffan
(författare)
-
Applications of microdialysis in studies of the adrenergic regulation of lipolysis in human skeletal muscle and adipose tissue
- 1998
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipolysis, i.e., hydrolysis of triaeylglycerol to free fatty acids and glycerol, is a central process in lipid metabolism, and the regulation of lipid metabolism is altered in several common disorders, such as diabetes, obesity and atherosclerosis. Lipolysis is regulated in a complex way, catecholamines and insulin are important hormones, acting stimulatory and inhibitory on lipid mobilization, respectively. Both catecholamines and insulin are vasoactive, which implies that effects of the hormones on local blood flow have to be considered in studies of lipolysis regulation. Microdialysis is a novel technique that allows continuous sampling and manipulation of the interstitial space of a number of tissues including muscle and adipose tissue. It is possible to simultaneously monitor metabolic substrate concentrations and relative changes in local blood flow. The aim of this thesis was to focus on methodological and physiological aspects of the in vivo adrenergic regulation of lipolysis in human skeletal muscle and adipose tissue. The influence of blood flow on adipose tissue glycerol levels was investigated in human subcutaneous adipose tissue in situ (Paper 1). The microdialysis technique proved beneficial studying pharmacological interference with lipolysis, and it was found that stimulation of blood flow under certain conditions may decrease the level of glycerol in the extracellular space of adipose tissue although the mobilization of glycerol from fat cells to this compartment is increased. Hence, changes in blood flow and glycerol should be considered together when adipose tissue lipolysis is investigated by microdialysis. Although it is well established in several mammalian species that ß-adrenoceptors play a major role in regulating lipolysis and thermogenesis in adipose tissue, the functional existence and role of this receptor subtype in man has been controversial. In paper II, we demonstrate the presence of a functional ß-adrenoceptor in vivo in man and, moreover, the co-existence with ß,- and ß-adrenoceptors, indicating a role in lipolysis regulation. The combined use of the atraumatic microdialysis technique and easy accessible adipose tissue is an attractive model system for pharmacological in vivo studies in humans. This setting was used to investigate the synergistic effect of forskolin, a direct activator of the catalytic subunit of adenylyl cyclase, on ß-adrenoceptor-mediated stimulation of lipolysis and blood flow in human adipose tissue in vivo (Paper III). It was found that local administration of forskolin and isoprenaline induce lipolysis and increase blood flow and that the effect of isoprenaline is potentiated by forskolin in vivo in man. It has been previously shown that the antilipolytic effect of insulin is primarily mediated by activation of phosphodiesterase 3B (PDE3B) in adipocytes. Various PDE inhibitors were applied locally to the abdominal subcutaneous fat as well as the gastrocnemius skeletal muscles during a hyperinsulinemic euglycemic condition (Paper IV). We report that insulin inhibits lipolysis in adipose tissue and skeletal muscle by various PDEs, suggesting a unique metabolic role of muscle lipolysis. In paper V, the relative differences in glycerol and lactate concentrations in muscle and adipose tissue were investigated. In addition, methodological issues regarding substrate recovery and microdialysis catheter contamination were addressed. A substantial mobilization of glycerol and lactate was recognized in both adipose tissue and skeletal muscle at rest. Glycerol and lactate production are influenced by hyperinsulinemia and hypoglycemia in both tissues. Adipose tissue appears to be the major site ot glycerol production, whereas skeletal muscle and fat may be equally important for lactate production. In conclusion, microdialysis is a valuable tool with exceptional advantages for in vivo metabolic studies in skeletal muscle and adipose tissue, and more so when variations in local blood flow is accounted for. A new ß-adrenoceptor was functionally demonstrated in vivo and the synergistic effect of a direct adenylyl cyclase activator on 13-adrenoceptor-mediated stimulation of lipolysis and blood flow was elucidated. Moreover, we suggest a unique regulation of lipolysis in skeletal muscle and report on the absolute concentrations of glycerol and lactate in human skeletal muscle and adipose tissue.
|
|
| 3. |
- Enoksson, Staffan, et al.
(författare)
-
Marked Re-Utilization of Free Fatty Acids During Activated Lipolysis in Human Skeletal Muscle.
- 2005
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:2, s. 1189-1195
-
Tidskriftsartikel (refereegranskat)abstract
- Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P < 0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.
|
|
| 4. |
- Kabir, Mohammad, 1974, et al.
(författare)
-
A Test Vehicle for RF/DC Evaluation and Destructive Testing Of Vertically Grown Nanostructures (VGCNS)
- 2011
-
Ingår i: Proceedings of the NT11 International Conference on the Science and Application of Nanotubes, Cambridge, UK, July 10-16, 2011.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have developed an RF test vehicle suitable for measuring DC and microwave performance of vertically grown carbon nanostructures (VGCNS) as via-interconnects. A first version of the interconnect test vehicles devices were designed, fabricated and characterized. The RF small signal (S-parameter) and large signal measurements show that carbon nanofibres can be used as interconnects in microwave circuit, even for power devices. The design of test vehicle employs a three metal layer concept, forming sequentially the ground, signal and device under test structures for characterization in a microstrip configuration. The structures as such consisted of interconnects of dimensions ranging from 50 nm to 100 µm diameter made of VGCNS. In the first version of the interconnect test vehicles, the interconnects were made of carbon nanofibers grown at 450 C. From SEM measurement we found that the resulting height was around 1.5-2 µm. Epoxy polymer SU-8 was employed by spinning on the device and a subsequent etch back process was carried out to open up the tip of the fibres to connect to consecutive interconnects with the third metallisation layer. After growing the nanofibres, it was observed, using SEM, that interconnect sizes smaller than 10 µm diameter suffered from parasitic growth and therefore the effective device dimension deviated from the initial design. We carried out small signal measurements using a vector network analyser for frequency ranging from 1 to 25 GHz, in order to characterise the transmission and reflection/absorption of the devices as function of their diameter size. The large signal evaluation was performed by measuring the gain compression of the devices. In addition destructive tests, aiming at testing the current carrying capability of the interconnect, have also been performed.The resistivity of interconnects was measured to vary varies from 0.2 µΩ·mm-1.3 mΩ·mm. Apparently, the device performance is considerably influenced by the fill factor of the interconnect with VGCNS. Small variations in fill factor (in %) provided a large variations in device resistivity. Furthermore, it was also observed that the resistance drops at higher power levels. RF conductivity of interconnects ranges from 5x10^3 S/m to 7x10^5 S/m. The average input power before interconnect destruction is larger than 25W with effective device diameter ranging from 3 µm to 100 µm interconnects. In addition, the average gain compression before interconnect destruction was found to be 0.6 dB. It was not possible to extract the conductivity value of an individual nanofiber using comparison to simulation data, since the devices might have suffered from parasitic growth as well as pinhole metal diffusion during top metal contact formation. This certainly affects the actual device dimension and properties. Nevertheless, the proof of concept of design and manufacturing a test vehicle for RF measurements of vertically grown nanostructures was achieved. We will report the findings and anomalies in the measured devices. Further improvement is expected in the coming test vehicle version.
|
|
