| First Author | Cochran BJ | Year | 2016 |
| Journal | Diabetologia | Volume | 59 |
| Issue | 9 | Pages | 1977-84 |
| PubMed ID | 27193916 | Mgi Jnum | J:236054 |
| Mgi Id | MGI:5804508 | Doi | 10.1007/s00125-016-3993-5 |
| Citation | Cochran BJ, et al. (2016) In vivo PET imaging with [(18)F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes. Diabetologia 59(9):1977-84 |
| abstractText | AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: Treatment of db/db mice with apoA-I for 2 h significantly improved both glucose tolerance (AUC 2574 +/- 70 mmol/l x min vs 2927 +/- 137 mmol/l x min, for apoA-I and PBS, respectively; p < 0.05) and insulin sensitivity (AUC 388.8 +/- 23.8 mmol/l x min vs 194.1 +/- 19.6 mmol/l x 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 x 10(-2) min(-1) vs 2.3 +/- 0.7 x 10(-2) min(-1), for apoA-I and PBS, respectively; p < 0.05) and an increased influx constant (3.7 +/- 0.6 x 10(-3) ml min(-1) g(-1) vs 2.0 +/- 0.3 x 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. CONCLUSIONS/INTERPRETATION: These findings indicate that apoA-I improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation. |
