Tags

Type your tag names separated by a space and hit enter

Cellular chromium enhances activation of insulin receptor kinase.
Biochemistry 2005; 44(22):8167-75B

Abstract

Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes.

Authors+Show Affiliations

Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908-0577, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15924436

Citation

Wang, Hong, et al. "Cellular Chromium Enhances Activation of Insulin Receptor Kinase." Biochemistry, vol. 44, no. 22, 2005, pp. 8167-75.
Wang H, Kruszewski A, Brautigan DL. Cellular chromium enhances activation of insulin receptor kinase. Biochemistry. 2005;44(22):8167-75.
Wang, H., Kruszewski, A., & Brautigan, D. L. (2005). Cellular chromium enhances activation of insulin receptor kinase. Biochemistry, 44(22), pp. 8167-75.
Wang H, Kruszewski A, Brautigan DL. Cellular Chromium Enhances Activation of Insulin Receptor Kinase. Biochemistry. 2005 Jun 7;44(22):8167-75. PubMed PMID: 15924436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular chromium enhances activation of insulin receptor kinase. AU - Wang,Hong, AU - Kruszewski,Allison, AU - Brautigan,David L, PY - 2005/6/1/pubmed PY - 2005/8/27/medline PY - 2005/6/1/entrez SP - 8167 EP - 75 JF - Biochemistry JO - Biochemistry VL - 44 IS - 22 N2 - Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/15924436/full_citation L2 - https://dx.doi.org/10.1021/bi0473152 DB - PRIME DP - Unbound Medicine ER -