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Vol 2, No 2 (2001): Practical Diabetology
Original articles (translated)
Published online: 2001-03-08
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Novel hepatoselective insulin analog

Fariba Shojaee-Moradie, James K. Powrie, Erik Sundermann, Mark W. Spring, Achim Schüttler, Dietrich Brandenburg, Mark W. Spring, Achim Schüttler, Dietrich Brandenburg, Mark W. Spring, Achim Schüttler, Dietrich Brandenburg
Diabetologia Praktyczna 2001;2(2):151-158.

open access

Vol 2, No 2 (2001): Practical Diabetology
Original articles (translated)
Published online: 2001-03-08

Abstract

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 B1 L-thyroxyl-insulin (B1-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-6,6-2H2]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, B1-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (~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, B1-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma half-life. 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.

Abstract

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 B1 L-thyroxyl-insulin (B1-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-6,6-2H2]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, B1-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (~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, B1-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma half-life. 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.
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Keywords

B1-T4-Ins insulin; NPH insulin; type 1 diabetes

About this article
Title

Novel hepatoselective insulin analog

Journal

Clinical Diabetology

Issue

Vol 2, No 2 (2001): Practical Diabetology

Pages

151-158

Published online

2001-03-08

Bibliographic record

Diabetologia Praktyczna 2001;2(2):151-158.

Keywords

B1-T4-Ins insulin
NPH insulin
type 1 diabetes

Authors

Fariba Shojaee-Moradie
James K. Powrie
Erik Sundermann
Mark W. Spring
Achim Schüttler
Dietrich Brandenburg
Mark W. Spring
Achim Schüttler
Dietrich Brandenburg
Mark W. Spring
Achim Schüttler
Dietrich Brandenburg

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