Title |
In vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes
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Published in |
Diabetologia, May 2016
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DOI | 10.1007/s00125-016-3993-5 |
Pubmed ID | |
Authors |
Blake J. Cochran, William J. Ryder, Arvind Parmar, Shudi Tang, Anthonin Reilhac, Andrew Arthur, Arnaud Charil, Hasar Hamze, Philip J. Barter, Leonard Kritharides, Steven R. Meikle, Marie-Claude Gregoire, Kerry-Anne Rye |
Abstract |
Type 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle. This study used kinetic modelling to investigate the impact of increasing plasma apoA-I levels on the metabolism of glucose in the db/db mouse model. Treatment of db/db mice with apoA-I for 2 h significantly improved both glucose tolerance (AUC 2574 ± 70 mmol/l × min vs 2927 ± 137 mmol/l × min, for apoA-I and PBS, respectively; p < 0.05) and insulin sensitivity (AUC 388.8 ± 23.8 mmol/l × min vs 194.1 ± 19.6 mmol/l × min, for apoA-I and PBS, respectively; p < 0.001). ApoA-I treatment also increased glucose uptake by skeletal muscle in both an insulin-dependent and insulin-independent manner as evidenced by increased uptake of fludeoxyglucose ([(18)F]FDG) from plasma into gastrocnemius muscle in apoA-I treated mice, both in the absence and presence of insulin. Kinetic modelling revealed an enhanced rate of insulin-mediated glucose phosphorylation (k 3) in apoA-I treated mice (3.5 ± 1.1 × 10(-2) min(-1) vs 2.3 ± 0.7 × 10(-2) min(-1), for apoA-I and PBS, respectively; p < 0.05) and an increased influx constant (3.7 ± 0.6 × 10(-3) ml min(-1) g(-1) vs 2.0 ± 0.3 × 10(-3) ml min(-1) g(-1), for apoA-I and PBS, respectively; p < 0.05). Treatment of L6 rat skeletal muscle cells with apoA-I for 2 h indicated that increased hexokinase activity mediated the increased rate of glucose phosphorylation. These findings indicate that apoA-I improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation. |
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Country | Count | As % |
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Australia | 1 | 17% |
France | 1 | 17% |
United States | 1 | 17% |
Canada | 1 | 17% |
Unknown | 2 | 33% |
Demographic breakdown
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Members of the public | 2 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 33 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 3 | 9% |
Student > Doctoral Student | 3 | 9% |
Professor | 3 | 9% |
Researcher | 3 | 9% |
Professor > Associate Professor | 3 | 9% |
Other | 7 | 21% |
Unknown | 11 | 33% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 9% |
Agricultural and Biological Sciences | 3 | 9% |
Neuroscience | 3 | 9% |
Other | 4 | 12% |
Unknown | 11 | 33% |