OBJECTIVE: To investigate whether human insulin (HI) and insulin analogues differ in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor A (IR-A) and the human insulin receptor B (IR-B) in vitro. METHODS: HI, short-acting insulin analogues (insulin aspart; insulin lispro) and long-acting insulin analogues (insulin glargine; insulin detemir) were compared by using kinase receptor activation (KIRA) bioassays specific for IGF-IR, IR-A or IR-B, respectively. These assays quantify ligand activity by measuring receptor auto-phosphorylation upon ligand binding. HI and insulin analogues were tested in a range from 0.1 to 100 nM. RESULTS: Short-acting analogues: Overall, short-acting insulin analogues did not differ substantially from HI, nor from each other. Insulin lispro was slightly more potent than HI and insulin aspart in activating the IGF-IR, only reaching statistical significance at 100 nM (p<0.01). Long-acting analogues: At <10 nM insulin glargine was as potent as HI in activating the IRs and IGF-IR. At 10-100 nM insulin glargine was significantly more potent than HI in activating the IR-B (p<0.05) and IGF-IR (p<0.001). Insulin glargine was more potent than insulin detemir in activating all three receptors (p<0.001). Insulin detemir was less potent than HI in activating the IRs at 1-10 nM (p<0.01) and IGF-IR at >1 nM (p<0.05). CONCLUSIONS: Insulin glargine was more potent in activating the IGF-IR than HI and insulin detemir. Since KIRA bioassays do not mimic the exact in vivo situation, further research is needed to find out whether our data have implications for clinical use of insulin glargine.
OBJECTIVE: To investigate whether humaninsulin (HI) and insulin analogues differ in their ability to activate the humanIGF-I receptor (IGF-IR), the humaninsulin receptor A (IR-A) and the humaninsulin receptor B (IR-B) in vitro. METHODS:HI, short-acting insulin analogues (insulin aspart; insulin lispro) and long-acting insulin analogues (insulinglargine; insulindetemir) were compared by using kinase receptor activation (KIRA) bioassays specific for IGF-IR, IR-A or IR-B, respectively. These assays quantify ligand activity by measuring receptor auto-phosphorylation upon ligand binding. HI and insulin analogues were tested in a range from 0.1 to 100 nM. RESULTS: Short-acting analogues: Overall, short-acting insulin analogues did not differ substantially from HI, nor from each other. Insulin lispro was slightly more potent than HI and insulin aspart in activating the IGF-IR, only reaching statistical significance at 100 nM (p<0.01). Long-acting analogues: At <10 nM insulinglargine was as potent as HI in activating the IRs and IGF-IR. At 10-100 nM insulinglargine was significantly more potent than HI in activating the IR-B (p<0.05) and IGF-IR (p<0.001). Insulinglargine was more potent than insulindetemir in activating all three receptors (p<0.001). Insulindetemir was less potent than HI in activating the IRs at 1-10 nM (p<0.01) and IGF-IR at >1 nM (p<0.05). CONCLUSIONS:Insulinglargine was more potent in activating the IGF-IR than HI and insulindetemir. Since KIRA bioassays do not mimic the exact in vivo situation, further research is needed to find out whether our data have implications for clinical use of insulinglargine.
Authors: A J Varewijck; J A M J L Janssen; M Vähätalo; L J Hofland; S W J Lamberts; H Yki-Järvinen Journal: Diabetologia Date: 2012-01-10 Impact factor: 10.122
Authors: Bo F Hansen; Tine Glendorf; Anne C Hegelund; Anders Lundby; Anne Lützen; Rita Slaaby; Carsten Enggaard Stidsen Journal: PLoS One Date: 2012-05-08 Impact factor: 3.240