S 15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus. Effect on pancreatic islets of insulin resistant animals.

A histological study has been conducted on pancreata from insulin resistant sand rats treated with S15261. As previously shown, standard laboratory chow induced dietary hyperinsulinaemia, insulin resistance and hyperlipaemia in sand rats (Psammomys obesus). Degranulation, vacuolization and even necrosis of beta-cells were observed in these animals. These changes were often accompanied by fibrosis and lymphocytic infiltration. Insulin and amylin immuno-reactivity of beta-cells was markedly decreased whilst glucagon secreting cells were localized now in the centre of the islets. Chronic treatment with S15261, a compound able to restore insulin sensitivity in insulin resistant animals, promoted the regranulation of the beta-cells and maintained the usual cytoarchitecture and integrity of the islets.

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 laboratory chow diet, they become overweight, develop hypertriglyceridaemia, hypercholesterolaemia, become insulin resistant, and ultimately diabetic. In the present study glucose intolerant animals, with very mild 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-cholesterol without any modification of HDL-cholesterol. In this study only female sand rats showed elevated plasma glucose levels, which were normalised by S15261. The compound also decreased plasma insulin levels both in male and female sand rats. An oral glucose tolerance test showed a major improvement in glucose tolerance in both male and female animals treated with S15261. These data confirm in another animal model the therapeutic benefits of S15261 in insulin resistant states.