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Diabetes 54:361-366, 2005
© 2005 by the American Diabetes Association, Inc.

Insulin Glulisine

Insulin Receptor Signaling Characteristics In Vivo

Anita M. Hennige, Rainer Lehmann, Cora Weigert, Klaus Moeschel, Myriam Schäuble, Elisabeth Metzinger, Reiner Lammers, and Hans-Ulrich Häring

From the University of Tuebingen, Department of Internal Medicine IV, Tuebingen, Germany

In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (LysB3, GluB29) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment.

Address correspondence and reprint requests to Prof. Hans-Ulrich Häring, University of Tuebingen, Department of Internal Medicine IV, D-72076, Tuebingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de

Abbreviations: IRS, insulin receptor substrate; MAP, mitogen-activated protein; PI, phosphatidylinositol


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[Abstract] [Full Text] [PDF]


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Copyright © 2005 by the American Diabetes Association.