S15261, A NOVEL AGENT FOR THE TREATMENT OF INSULIN-RESISTANCE - STUDIES ON PSAMMOMYS-OBESUS

S15261 is a novel compound that has been proposed for the treatment of insulin resistance syndrome. We have studied the effects of this drug in insulin resistant sand rats (Psammomys obesus). When sand rats are transferred from their natural desert environment and placed on a lab oratory chow diet, they become overweight, develop hypertriglyceridaem ia, hypercholesterolaemia, become insulin resistant, and ultimately di abetic. In the present study glucose intolerant animals, with very mil d if any hyperglycaemia were used. Chronic treatment for a month with S15261 normalised plasma levels of triglycerides and cholesterol. The effects on cholesterol were the result of a decrease in LDL-and VLDL-c holesterol without any modification of HDL-cholesterol. In this study only female Sand rats showed elevated plasma glucose levels, which wer e normalised by S15261. The compound also decreased plasma insulin lev els both in male and female sand rats. An oral glucose tolerance test showed a major improvement in glucose tolerance in both male and femal e animals treated with S15261. These data confirm in another animal mo del the therapeutic benefits of S15261 in insulin resistant states.