Characteristics of signalling properties mediated by long-acting insulin analogue glargine and detemir in target cells of insulin.

Article Details

Citation

Wada T, Azegami M, Sugiyama M, Tsuneki H, Sasaoka T

Characteristics of signalling properties mediated by long-acting insulin analogue glargine and detemir in target cells of insulin.

Diabetes Res Clin Pract. 2008 Sep;81(3):269-77. doi: 10.1016/j.diabres.2008.05.007. Epub 2008 Jun 27.

PubMed ID
18585815 [ View in PubMed
]
Abstract

Glargine and detemir are long-acting human insulin analogues with a smooth peakless profile of action. Although their binding affinities to the insulin receptor have been studied, little is known about the subsequent signalling properties activated after the binding. We directly compared intracellular signalling properties of them in various cultured cells. Regarding the metabolic signalling, glargine and insulin-induced comparable dose-dependent phosphorylation of insulin receptor, IRS-1, Akt, and GSK3, whereas detemir-induced kinetics were markedly lower in 3T3-L1 adipocytes and L6 myocytes. A similar pattern of phosphorylation induction was observed in primary hepatocytes and vascular smooth muscle cells (VSMCs). Because of the binding of detemir to albumin with high affinity, the phosphorylation kinetics and glucose uptake of detemir, but not glargine, decreased with increasing concentrations of BSA. Concerning the mitogenic properties, glargine and insulin-induced comparable dose-dependent phosphorylation of MAP kinase (MAPK) and 5-bromo-2'-deoxyuridine (BrdU) incorporation. Detemir-induced phosphorylation of MAPK was apparently reduced, whereas it stimulated BrdU incorporation with relatively similar dose-dependent manner in VSMCs. These results indicate that glargine has comparable properties to human insulin in metabolic and mitogenic signalling and action. In contrast, detemir-induced metabolic signaling is less potent in all cell types studied, and is reduced further by increasing concentrations of albumin.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Insulin detemirInsulin receptorProteinHumans
Yes
Agonist
Details
Insulin glargineInsulin receptorProteinHumans
Yes
Agonist
Details