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Horm Metab Res 2003; 35(10): 617-624
DOI: 10.1055/s-2003-43510
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

The Effects of K-111, a New Insulin-sensitizer, on Metabolic Syndrome in Obese Prediabetic Rhesus Monkeys

N.  L.  Bodkin1 , J.  Pill2 , K.  Meyer2 , B.  C.  Hansen1
  • 1Obesity and Diabetes Research Center, School of Medicine, Dept. of Physiology, University of Maryland, Baltimore, MD, USA
  • 2Roche Diagnostics GmbH, Mannheim, Germany
Further Information

Publication History

Received 14 August 2002

Accepted after revision 18 June 2003

Publication Date:
07 November 2003 (online)

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Abstract

K-111, formerly BM 17.0744, (2,2-dichloro-12-(4-chlorophenyl)-dodecanoic acid) is a new insulin-sensitizer with peroxisome proliferator-activated receptor (PPAR) alpha activity but without PPAR gamma activity. We determined the efficacy of K-111 in non-human primates in increasing insulin-stimulated glucose uptake and improving metabolic syndrome, assessing the general health-related effects. Six adult male obese normoglycemic prediabetic and insulin-resistant rhesus monkeys were studied on vehicle and following K-111 treatment (four-week chronic dosing each of 3 doses: 1, 3, and 10 mg/kg/d) with assessment of changes in substrate, hormone, and blood pressure measurements and alterations in insulin sensitivity using the euglycemic, hyperinsulinemic clamp technique. K-111 led to significantly decreased body weight and improved hyperinsulinemia, insulin sensitivity, hypertriglyceridemia, and HDL-cholesterol levels without adipogenesis or significant effects on fasting glucose, 24-hour urine glucose excretion, systolic or diastolic blood pressure, plasma fibrinogen, total cholesterol, or chemistry and hematology profile. These benefits are similar to the health-improving effects of calorie restriction, providing preliminary evidence that K-111 has excellent potential as a calorie-restriction mimetic agent. These results indicate the necessity of future study of K-111 for metabolic syndrome in humans, and suggest potential in reducing the risks of diabetes and cardiovascular disease.

Key words

K-111 - BM 17.0744 - Hyperinsulinemia - Insulin resistance syndrome - Metabolic syndrome X - Dyslipidemia - Type 2 diabetes mellitus - Peroxisome proliferator-activated receptor α - Thiazolidinedione - Calorie restriction mimetic

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N. L. Bodkin, Ph. D.

Obesity and Diabetes Research Center, Dept. of Physiology, University of Maryland ·

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