Insulin and its analogs: actions via insulin and IGF receptors.

Article Details

Citation

Vigneri R, Squatrito S, Sciacca L

Insulin and its analogs: actions via insulin and IGF receptors.

Acta Diabetol. 2010 Dec;47(4):271-8. doi: 10.1007/s00592-010-0215-3. Epub 2010 Aug 21.

PubMed ID
20730455 [ View in PubMed
]
Abstract

Insulin analogs are artificially modified insulin molecules that allow better metabolic controls of diabetes through either more rapid or more prolonged activity. The interaction of insulin analogs with the insulin receptor isoforms (IR-A and IR-B) and with the IGF-I receptor (IGF-IR) is similar but not identical to that of insulin, and therefore, their biological effects do not always reproduce insulin actions in terms of quantity, quality and timing. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar, but not identical, to those of insulin via IR-A, IR-B and IGF-IR. In contrast, long-acting analogs behave in a more different way relative to insulin. Although data are not homogeneous and observations on the more recently introduced detemir are scarce, both glargine and detemir often show a decreased binding to IR and increased binding to IGF-IR. Also, intracellular signaling is different with respect to insulin, with a prevalent activation of the ERK rather than the AKT pathway. Finally, an increased mitogenic response has often been observed with these analogs in a variety of cell models. Of course, in vitro studies do not necessarily reflect what occurs in patients, due to the different metabolism of analogs in vivo and their interaction with components of the extracellular environment. After many years of analog's use, observations in patients indicate that insulin analogs are both effective and safe. Prospective clinical studies, however, may add further useful information on the issue of the insulin analogs' possible differences with respect to native insulin.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Insulin aspartInsulin-like growth factor 1 receptorProteinHumans
Unknown
Activator
Details