Effect of acute and sub-chronic administration of the imidazoline compound S 22068 on in vivo glucose and insulin responses in normal lean CBA/Ca mice.

Acute S 22068 (24 mg/kg po) improved glucose tolerance and increased insulin sensitivity, assessed as the acute blood glucose response to exogenous insulin. The same acute dose did not stimulate insulin secretion or induce hypoglycemia in fed animals. Comparison of acute S 22068 to equipotent doses (with respect to effect on glucose tolerance) of gliclazide (2 mg/kg) and metformin (60 mg/kg) found S 22068 to be similar to metformin with respect to its effects on basal glucose levels (BGL) and insulin sensitivity. This also suggests that S 22068 acts by a mechanism which does not involve insulin release. Acute or sub-chronic S 22068 (14 days at 25 mg/day) had no effect on brown adipose tissue (BAT) or white adipose tissue (WAT) lipogenesis, an insulin-sensitive metabolic pathway. Sub-chronic treatment with S 22068 did not alter body weight (BW) or food intake, and resulted in tolerance to its effects on glucose metabolism and insulin sensitivity. These findings suggest that S 22068 is similar in effect to metformin, and is not insulinogenic, in contrast to the sulfonylureas or putative I(3) imidazoline site ligands.