The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese prediabetic rhesus monkeys.

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.

• Authors: N L Bodkin, J Pill, K Meyer, B C Hansen
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 35 Issue 10 Pg. 617-24 (Oct 2003) ISSN: 0018-5043 [Print] Germany
• PMID: 14605998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid
• Blood Glucose
• Cholesterol, HDL
• Insulin
• Lauric Acids
• Triglycerides

Topics

• Animals
• Blood Glucose (analysis)
• Blood Pressure
• Cholesterol, HDL (blood)
• Diabetes Mellitus, Type 2 (etiology, prevention & control)
• Fasting
• Glucose Clamp Technique
• Glycosuria
• Insulin (blood, pharmacology)
• Insulin Resistance
• Lauric Acids (administration & dosage)
• Macaca mulatta
• Male
• Metabolic Syndrome (drug therapy)
• Obesity (complications, physiopathology)
• Prediabetic State (drug therapy)
• Triglycerides (blood)
• Weight Loss