SPLANCHNIC EXTRACTION AND POTENCY OF NN304 VS H INSULIN

$0M01FY2000RRNIH

University Of Southern California, Los Angeles CA

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Abstract

In this study in normal subjects (n=20), we will examinethe dynamic relationship between the fatty acid acylated insulin, [LysB29-tetradecanoyl, des-(B30) human insulin], or NN304, and the rate of heptic gluclose production, measured directly with the artiovenous difference technique via heptatic vein catherization. We will also examine the potency (steady state action based upon gluclose turnover and suppression of non-esterified fatty acids) of NN304 in comparison to an equimolar intravenous continous infusion of native insulin (Novolin-R). We will directly determine the splanchic (hepatic) extraction of NN304, native insulin, and C-peptide by the liver via heptic vein catherization. Finally, we will determine to what extent any difference in potency between NN304 and human insulin can be explained by the hepatic extraction of NN304.

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