Targeting low-density lipoprotein and dysmetabolism in type 2 diabetes mellitus.
Targeting low-density lipoprotein and dysmetabolism in type 2 diabetes mellitus.
复制标题
针对 2 型糖尿病的低密度脂蛋白和代谢障碍。
DOI：
10.1161/atvbaha.114.303171
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Goldberg,Ronald
中科院分区：
文献类型：
--
作者：
Goldberg,Ronald
478 Arterioscler Thromb Vasc Biol March 2014 those with baseline hsCRP levels> 2.0 mg/l in which there was a 43% to 65% reduction. These observations suggest that like statins, ETC-1002 has anti-inflammatory properties that may be associated with CVD benefit beyond LDL reduction particularly in those with heightened subclinical inflammation. However, unlike with statins, the anti-inflammatory effect of ECT-1002 may be more closely tied to improvements in the dysmetabolism of type 2 diabetes mellitus. The principal metabolic role of AMPK is as master cellular fuel gauge, switching metabolism in ATP-depleted states, for example, exercise, from ATP-consuming activities, such as hepatic glucose production and lipid synthesis, to ATP-producing activities, such as fatty acid oxidation. Recently, activation of AMPK by ETC-1002 complemented by ACL inhibition in rodent models of obesity has been shown to produce broad anti-inflammatory effects such as suppression of leukocyte homing and reduced adipose inflammation, as well as lower hepatic lipids, and glucose and insulin levels. 6, 10 Thus, by activating AMPK and inhibiting ACL, ETC-1002 may help to ameliorate steatosis, inflammation, and insulin resistance as has been shown with pioglitazone and metformin therapies. 11, 12Although there were downward trends, Gutierrez et al did not find significant lowering of fasting, postprandial, and hourly plasma glucose levels or during continuous glucose monitoring, nor of fasting insulin after 4 weeks of ETC-1002 therapy. Daily peak and postprandial glucose levels in the obese subgroup were significantly lower, and there was more frequent reporting of hyperglycemia as an adverse event in the placebo versus ETC-1002 groups. The fact that glucose levels did not rise in the placebo group despite discontinuation of metformin therapy suggests that lifestyle changes during the in-house dosing period contributed to improved glycemic control making it difficult to interpret these results. The effects of ETC-1002 on insulin sensitivity and hepatic glucose production measured directly and under steady-state conditions are clearly needed. Thus, although these preliminary findings do not allow us to conclude that ETC-1002 has a clinically useful antihyperglycemic effect in diabetic subjects, together with previously published data they provide a basis for anticipating that this agent, in contrast to statins, does not aggravate glucose intolerance and, like metformin, may reduce hepatic glucose production and improve insulin sensitivity.
影响因子：
15.9
作者：
Dugan, Laura L.;You, Young-Hyun;Sharma, Kumar
通讯作者：
Sharma, Kumar
影响因子：
5.8
作者：
Goldberg, R.;Temprosa, M.;Barrett-Connor, E.
通讯作者：
Barrett-Connor, E.