The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese prediabetic rhesus monkeys.
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.
Bodkin
N L
NL
Obesity and Diabetes Research Center, School of Medicine, Dept. of Physiology, University of Maryland, Baltimore, MD 21201, USA. nbodkin678@aol.como
Pill
J
J
Meyer
K
K
Hansen
B C
BC
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000517:prevention & control; D005215:Fasting; D015309:Glucose Clamp Technique; D006029:Glycosuria; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D007850:Lauric Acids / Q000008:administration & dosage*; D008253:Macaca mulatta; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D011236:Prediabetic State / Q000188:drug therapy*; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss
C116893:2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D007850:Lauric Acids; D014280:Triglycerides