Pre-clinical methods for the determination of insulin sensitivity.

We compared the hyperinsulinaemic euglycaemic glucose clamping (HEGC) procedure and the rapid insulin sensitivity test (RIST) to characterize insulin sensitivity in anaesthetized rats. The changes in insulin sensitivity were then supplemented with the direct measurement of insulin-stimulated glucose uptake using tissue accumulation of radioactive 2-deoxyglucose in skeletal muscle samples obtained from animals undergone either procedure. Studies of the recently described endogenous insulin sensitizer mechanism termed hepatic insulin sensitizing (HISS) mechanism, by the two methods yielded data for evaluation.

BGP-15 - a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity.

Nephrotoxicity is one of the major dose limiting side effects of cisplatin chemotherapy. The antitumor and toxic effects are mediated in part by different mechanisms, thus, permitting a selective inhibition of certain side effects. The influence of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) - a poly(ADP-ribose) polymerase (PARP) inhibitor - on the nephrotoxicity and antitumor efficacy of cisplatin has been evaluated in experimental models.