Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor.

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Sorensen AR, Stidsen CE, Ribel U, Nishimura E, Sturis J, Jonassen I, Bouman SD, Kurtzhals P, Brand CL

Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor.

Diabetes Obes Metab. 2010 Aug;12(8):665-73. doi: 10.1111/j.1463-1326.2010.01206.x.

PubMed ID

20590743 [ View in PubMed

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Abstract

AIM: To compare the properties of insulin detemir with human insulin or insulin aspart in various in vitro and in vivo experiments, thereby highlighting the importance of performing dose-response studies when investigating insulin analogues, in this study specifically insulin detemir. METHODS: Displacement of membrane-associated insulin receptors from human and rat hepatocytes, and from Chinese Hamster Ovary cells over-expressing human insulin receptor (CHO-hIR) at varying albumin concentrations is measured. Lipogenesis in primary rat adipocytes over time and the effects in the simultaneous presence of insulin detemir and human insulin or insulin aspart are assessed. The hyperinsulinaemic euglycaemic clamp technique in rats is used to establish dose-response curves for multiple metabolic endpoints and to investigate the effects of the simultaneous presence of insulin detemir and human insulin. RESULTS: Both in vitro and in vivo, insulin detemir shows full efficacy and right-shifted parallel dose-response curves compared with human insulin. The potency estimates are different between the in vivo and in vitro conditions and among different in vitro conditions, that is the potency decreases in vitro with increasing albumin concentration. The effects of insulin detemir and human insulin are additive both in vitro and in vivo. CONCLUSIONS: Insulin detemir is fully efficacious compared with human insulin on all metabolic endpoints measured in vitro and in vivo. The fact that the potency estimates are method-dependent emphasizes the importance of establishing full dose-response relationships when characterizing insulin detemir.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Insulin detemir	Insulin receptor	Protein	Humans	Yes	Agonist	Details