IC50: 5.01 nmol/L for insulin receptor

Insulin is a peptide hormone produced by beta cells in pancreas. Insulin has been found to stimulate glucose uptake into muscle and adipose tissue, which is central to the maintenance of whole body glucose homeostasis. Autoimmune destruction of the β-cells in pancreas leads to a lack of insulin production and the development of type I and II diabetes mellitus.

In vitro: Methotrexate (MTX) was found to be linked to insulin covalently. As effectively as insulin, insulin-MTX complex competed with 125I-insulin for insulin receptor. It was found that IC50 and Ki for insulin-MTX were 93.82 nM and 91.88 nM, respectively, whereas those for insulin were 5.01 nM and 4.85 nM, respectively [1].

In vivo: Previous study showed that insulin-stimulated glucose uptake in extensor muscles from SJL mice was reduced, but the basal uptake rates were not different. In another mouse study, knockdown of TC10α but not TC10β in 3T3-L1 adipocytes resulted in a inhibition of both insulin-stimulated glucose uptake and GLUT4 translocation [2].

Clinical trial: Clinical study shows that when insulin levels fails, diabetes mellitus can happen. Thus, insulin is medically used to treat some forms of diabetes mellitus. Biosynthetic human insulin for clinical use is manufactured by recombinant DNA technology. Insulin is often taken as subcutaneous injections . Morevoer, inhaled insulin is currently also available in U.S. market (https://en.wikipedia.org/wiki/Insulin#Medication_uses).

References:
[1] Ou X,Kuang A,Liang Z,Peng X,Zhong Y.? The binding characteristics of insulin-MTX to insulin receptor. Hua Xi Yi Ke Da Xue Xue Bao.2001 Dec;32(4):538-40.
[2] Leney SE,Tavaré JM.? The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets. J Endocrinol.2009 Oct;203(1):1-18.