LAPS Insulin115: A novel ultra-long-acting basal insulin with a unique action profile

Diabetes, Obesity & Metabolism
Nina WronkowitzJürgen Eckel

Abstract

To conduct a comprehensive pre-clinical study of the novel ultra-long acting insulin analogue LAPS Insulin115. Pharmacokinetic/pharmacodynamic studies comparing LAPS Insulin115 with other basal insulins were conducted in genetically diabetic (db/db) mice. Insulin signalling in the major target organs was analysed using Western blot after single subcutaneous injection in wild-type male Wistar rats. Using in vitro assays we analysed transendothelial transport, insulin receptor (IR) interaction, and the mitogenic and metabolic properties of LAPS Insulin115. Furthermore, IR downregulation after long-term exposure to high concentrations of LAPS Insulin115 was analysed using an in vitro desensitization/resensitization model. The novel Fc-conjugated insulin derivative LAPS Insulin115 showed an extensively prolonged pharmacokinetic and pharmacodynamic profile in rodents. Despite its size of 59 kDa, LAPS Insulin115 passes the vascular endothelial barrier and induces insulin signalling in all major target tissues in rats. In vitro, LAPS Insulin115 showed a very slow onset of action because of its reduced IR affinity; however, after long-term stimulation it was equipotent in respect to its metabolic potency and showed no increased mitogen...Continue Reading

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Citations

May 29, 2018·Diabetic Medicine : a Journal of the British Diabetic Association·R Herring, D D L Russell-Jones
Jun 15, 2017·The Journal of Endocrinology·Paul MillarVictor A Gault
Oct 1, 2019·American Journal of Therapeutics·Simona Cernea, Itamar Raz
Oct 1, 2019·American Journal of Therapeutics·Pablo Aschner
Feb 14, 2018·Diabetes Technology & Therapeutics·Satish K GargH Kaan Akturk
Nov 8, 2020·Protein Engineering, Design & Selection : PEDS·Christine FaustThomas Langer
Dec 6, 2020·Biologicals : Journal of the International Association of Biological Standardization·Daejin KimDae Kyong Kim
Mar 9, 2021·Frontiers in Pharmacology·Nuria ArdaizPedro Berraondo
Nov 3, 2020·Molecular Metabolism·Thomas Hoeg-Jensen
Jun 22, 2021·Trends in Pharmacological Sciences·Peter KurtzhalsThomas Kjeldsen
Jun 29, 2021·The Lancet. Diabetes & Endocrinology·Michael A NauckJuris J Meier
Jan 29, 2020·Bioconjugate Chemistry·Arnab RudraRobert Langer
Aug 25, 2021·Molecular Metabolism·Mark A JarosinskiMichael A Weiss
Dec 2, 2021·The Journal of Clinical Endocrinology and Metabolism·Mark A JarosinskiMichael A Weiss

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