Harbor Therapeutics, Inc., San Diego, California, USA.
Obesity (Silver Spring). 2013 Sep;21(9):E343-9. doi: 10.1002/oby.20207. Epub 2013 May 13.
To study the activity of HE3286 (17α-ethynylandrost-5-ene-3β,7β,17β-triol), an anti-inflammatory sterol that is active in models of obesity-induced inflammation and insulin resistance in high body mass index (BMI) subjects with impaired glucose tolerance (IGT).
HE3286 was explored in high BMI IGT subjects using hyperinsulinemic, euglycemic clamp studies.
In insulin-resistant subjects, HE3286 significantly increased day 29 insulin-stimulated glucose disposal and HDL cholesterol, and decreased C-reactive protein (CRP) compared to placebo. For HE3286, change in M value showed a significant negative correlation with baseline M value. Subjects with baseline M value below the median (4.2 mg/kg/min) had significantly lower adiponectin and higher lipopolysaccharide-stimulated peripheral blood mononuclear cell cytokine secretion. After 28 days of HE3286 treatment, adiponectin levels were significantly increased in insulin-resistant (baseline M < 4.2), but not insulin-sensitive (baseline M > 4.2) subjects, compared to placebo.
HE3286 significantly increased the frequency of subjects with increased insulin-stimulated glucose disposal and HDL, and decreased CRP compared to placebo, in insulin-resistant, but not insulin-sensitive subjects. Thus, HE3286 may preferentially benefit insulin-resistant, inflamed, high BMI IGT subjects.
研究 HE3286（17α-乙炔基雄甾-5-烯-3β,7β,17β-三醇）的活性，这是一种抗炎固醇，在高体重指数（BMI）、葡萄糖耐量受损（IGT）的肥胖诱导炎症和胰岛素抵抗模型中具有活性。
采用高 BMI、IGT 受试者的高胰岛素、正常血糖钳夹研究探索 HE3286。
在胰岛素抵抗受试者中，与安慰剂相比，HE3286 显著增加了第 29 天胰岛素刺激的葡萄糖处置和高密度脂蛋白胆固醇（HDL），并降低了 C 反应蛋白（CRP）。对于 HE3286，M 值的变化与基线 M 值呈显著负相关。基线 M 值低于中位数（4.2mg/kg/min）的受试者，脂联素水平显著降低，脂多糖刺激的外周血单个核细胞细胞因子分泌水平显著升高。与安慰剂相比，在胰岛素抵抗（基线 M<4.2）受试者中，经过 28 天的 HE3286 治疗后，脂联素水平显著升高，但在胰岛素敏感（基线 M>4.2）受试者中没有显著升高。
与安慰剂相比，HE3286 显著增加了胰岛素抵抗但不是胰岛素敏感受试者中胰岛素刺激的葡萄糖处置和 HDL 增加的频率，并降低了 CRP。因此，HE3286 可能优先使胰岛素抵抗、炎症、高 BMI、IGT 受试者受益。
