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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans.

OBJECTIVE: To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. RESEARCH DESIGN AND METHODS: Five normal human subjects received a subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. RESULTS: After subcutaneous administration, Bl-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (approximately 86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P < 0.05). CONCLUSIONS: When injected subcutaneously into normal human subjects, Bl-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma halflife. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used.[1]


  1. Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans. Shojaee-Moradie, F., Powrie, J.K., Sundermann, E., Spring, M.W., Schüttler, A., Sönksen, P.H., Brandenburg, D., Jones, R.H. Diabetes Care (2000) [Pubmed]
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