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

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

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adult
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Blood Glucose / metabolism
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Cholesterol, HDL / blood
  • Cytokines / metabolism
  • Dehydroepiandrosterone / analogs & derivatives*
  • Dehydroepiandrosterone / pharmacology
  • Dehydroepiandrosterone / therapeutic use
  • Double-Blind Method
  • Female
  • Glucose Intolerance / drug therapy*
  • Glucose Intolerance / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Insulin / metabolism*
  • Insulin Resistance*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides
  • Male
  • Obesity / blood
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism

Substances

  • 17-ethynyl-5-androstene-3, 7, 17-triol
  • Adiponectin
  • Anti-Inflammatory Agents
  • Blood Glucose
  • Cholesterol, HDL
  • Cytokines
  • Hypoglycemic Agents
  • Insulin
  • Lipopolysaccharides
  • Dehydroepiandrosterone
  • C-Reactive Protein