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| 2. |
- Musi, N., et al.
(författare)
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AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise
- 2001
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Ingår i: Diabetes. - Alexandria, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 50:5, s. 921-927
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-stimulated GLUT4 translocation is impaired in people with type 2 diabetes. In contrast, exercise results in a normal increase in GLUT4 translocation and glucose uptake in these patients. Several groups have recently hypothesized that exercise increases glucose uptake via an insulin-independent mechanism mediated by the activation of AMP-activated protein kinase (AMPK). If this hypothesis is correct, people with type 2 diabetes should have normal AMPK activation in response to exercise. Seven subjects with type 2 diabetes and eight matched control subjects exercised on a cycle ergometer for 45 min at 70% of maximum workload. Biopsies of vastus lateralis muscle were taken before exercise, after 20 and 45 min of exercise, and at 30 min postexercise. Blood glucose concentrations decreased from 7.6 to 4.77 mmol/l with 45 min of exercise in the diabetic group and did not change in the control group. Exercise significantly increased AMPK α2 activity 2.7-fold over basal at 20 min in both groups and remained elevated throughout the protocol, but there was no effect of exercise on AMPK α1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK α1, α2, and β1 in muscle compared with control subjects. AMPK α2 was shown to represent approximately two-thirds of the total a mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK α2 activity and normal expression of the α1, α2 and β1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes.
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| 4. |
- Kuhl, JE, et al.
(författare)
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Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle
- 2006
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 290:6, s. E1296-E1303
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Tidskriftsartikel (refereegranskat)abstract
- The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased V̇o2 maxby 13% and decreased intra-abdominal fat by 17%. Significant decreases (25–30%) in the concentration of malonyl-CoA were observed after training, 24–36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α (PGC-1α), a regulator of transcription that has been linked to the mediation of MCD expression by PPARα, was also increased (3-fold). In studies also conducted 24–36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1α-mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.
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| 6. |
- Musi, N., et al.
(författare)
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Metformin increases AMP-activated-protein-kinase activity in skeletal of subjects with type 2 diabetes
- 2002
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Ingår i: Diabetes. - Alexandra, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 51:7, s. 2074-2081
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Tidskriftsartikel (refereegranskat)abstract
- Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK α2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK α2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK α2.
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| 7. |
- Musi, R., et al.
(författare)
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Techno-economic analysis of concentrated solar power plants in terms of levelized cost of electricity
- 2017
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Ingår i: SOLARPACES 2016. - : American Institute of Physics (AIP). - 9780735415225
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Konferensbidrag (refereegranskat)abstract
- Levelized Cost of Electricity (LCOE) is an important metric which provides one way to compare the economic competitiveness of different electricity generation systems, calculated simply by dividing lifetime costs by lifetime production. Hidden behind the simplicity of this formula are various assumptions which may significantly alter results. Different LCOE studies exist in the literature, although their assumptions are rarely explicitly stated. This analysis gives all formulas and assumptions which allow for inter-study comparisons. The results of this analysis indicate that CSP LCOE is reducing markedly over time and that given the right location and market conditions, the SunShot 6¢/kWh 2020 target can be reached. Increased industrial cooperation is needed to advance the CSP market and continue to drive down LCOE. The results also indicate that there exist a country and technology level learning effect, either when installing an existing CSP technology in a new country or when using a new technology in an existing CSP country, which seems to impact market progress.
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| 8. |
- Musi, R., et al.
(författare)
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Techno-economic optimization of a scaled-up solar concentrator combined with CSPonD thermal energy storage
- 2017
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Ingår i: SolarPACES 2016. - : American Institute of Physics (AIP). - 9780735415225
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Konferensbidrag (refereegranskat)abstract
- A molten salt direct absorption receiver, CSPonD, used to simultaneously collect and store thermal energy is being tested by Masdar Institute and MIT in Abu Dhabi, UAE. Whilst a research-scale prototype has been combined with a beam-down tower in Abu Dhabi, the original design coupled the receiver with a hillside heliostat field. With respect to a conventional power-tower setup, a hillside solar field presents the advantages of eliminating tower costs, heat tracing equipment, and high-pressure pumps. This analysis considers the industrial viability of the CSPonD concept by modeling a 10 MWe up-scaled version of a molten salt direct absorption receiver combined with a hillside heliostat field. Five different slope angles are initially simulated to determine the optimum choice using a combination of lowest LCOE and highest IRR, and sensitivity analyses are carried out based on thermal energy storage duration, power output, and feed-in tariff price. Finally, multi-objective optimization is undertaken to determine a Pareto front representing optimum cases. The study indicates that a 40° slope and a combination of 14 h thermal energy storage with a 40-50 MWe power output provide the best techno-economic results. By selecting one simulated result and using a feed-in tariff of 0.25 /kWh, a competitive IRR of 15.01 % can be achieved.
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