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Obesity (Silver Spring). 2013 Sep;21(9):E343-9. doi: 10.1002/oby.20207. Epub 2013 May 13.

A synthetic anti-inflammatory sterol improves insulin sensitivity in insulin-resistant obese impaired glucose tolerance subjects.

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1
Harbor Therapeutics, Inc., San Diego, California, USA.

Abstract

OBJECTIVE:

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).

DESIGN AND METHODS:

HE3286 was explored in high BMI IGT subjects using hyperinsulinemic, euglycemic clamp studies.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
23670958
DOI:
10.1002/oby.20207
[Indexed for MEDLINE]
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